POPULARITY
Are you interested in urban nature futures? Summary of the article titled Nature futures for the urban century: Integrating multiple values into urban management from 2022 by Andressa V. Mansur, Robert I. McDonald, Burak Güneralp, HyeJin Kim, Jose A. Puppim de Oliveira, Corey T. Callaghan, Perrine Hamel, Jan J. Kuiper, Manuel Wolff, Veronika Liebelt, Inês S. Martins, Thomas Elmqvist, and Henrique M. Pereira, published in the Environmental Science and Policy journal. This is a great preparation to our next interview with Junaid Islam in episode 286 talking about the importance of non-tech zones in the city even though being a technology advocate. Since we are investigating the future of cities, I thought it would be interesting to see how we can integrate nature into our urban futures. This article presents the Urban Nature Futures Framework (UNFF) to help cities envision sustainable futures by integrating different perspectives on the role of nature in urban development, addressing ecological, social, and cultural values. Find the article through this link. Abstract: There is an emerging consensus that the health of the planet depends on the coexistence between rapidly growing cities and the natural world. One strategy for guiding cities towards sustainability is to facilitate a planning process based on positive visions for urban systems among actors and stakeholders. This paper presents the Urban Nature Futures Framework (UNFF), a framework for scenario building for cities that is based on three Nature Futures perspectives: Nature for Nature, Nature for Society, and Nature as Culture. Our framework engages stakeholders with envisioning the three Nature Futures perspectives through four components using participatory methods and quantitative models: identification of the socio-ecological feedbacks in cities, assessment of indirect impacts of cities on biodiversity, development of multi-scale indicators, and development of scenarios. Stakeholders in cities may use this framework to explore different options for integrating nature in its various manifestations within urban areas and to assess how different community preferences result in various cityscapes and distribution of associated benefits from nature among urban dwellers across multiple scales. Connecting episodes you might be interested in: No.244 - Interview with Joe Glesta about urban greenery's benefits for reducing heat island effects No.280 - Interview with Hudson Worsley about urban tree management You can find the transcript through this link. What wast the most interesting part for you? What questions did arise for you? Let me know on Twitter @WTF4Cities or on the wtf4cities.com website where the shownotes are also available. I hope this was an interesting episode for you and thanks for tuning in. Music by Lesfm from Pixabay
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Dispelling the Anthropic Shadow, published by Eli Rose on September 9, 2024 on The Effective Altruism Forum. This is a linkpost for Dispelling the Anthropic Shadow by Teruji Thomas. Abstract: There are some possible events that we could not possibly discover in our past. We could not discover an omnicidal catastrophe, an event so destructive that it permanently wiped out life on Earth. Had such a catastrophe occurred, we wouldn't be here to find out. This space of unobservable histories has been called the anthropic shadow. Several authors claim that the anthropic shadow leads to an 'observation selection bias', analogous to survivorship bias, when we use the historical record to estimate catastrophic risks. I argue against this claim. Upon a first read, I found this paper pretty persuasive; I'm at >80% that I'll later agree with it entirely, i.e. I'd agree that "the anthropic shadow effect" is not a real thing and earlier arguments in favor of it being a real thing were fatally flawed. This was a significant update for me on the issue. Anthropic shadow effects are one of the topics discussed loosely in social settings among EAs (and in general open-minded nerdy people), often in a way that assumes the validity of the concept[1]. To the extent that the concept turns out to be completely not a thing - and for conceptual rather than empirical reasons - I'd find that an interesting sociological/cultural fact. 1. ^ It also has a tag on the EA Forum. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org
Abstract: There are many reasons why a narrator may choose to provide or withhold the names of various characters. This article hypothesizes that Mormon intentionally omitted the name of a key character from the book of Helaman related to the origin of the Gaddianton robbers. While it is not possible to know exactly what information […] The post Nameless: Mormon's Dramatic Use of Omission in Helaman 2 first appeared on The Interpreter Foundation.
ePub feed of Interpreter: A Journal of Latter-day Saint Faith and Scholarship
Abstract: There are many reasons why a narrator may choose to provide or withhold the names of various characters. This article hypothesizes that Mormon intentionally omitted the name of a key character from the book of Helaman related to the origin of the Gaddianton robbers. While it is not possible to know exactly what information […] The post Nameless: Mormon's Dramatic Use of Omission in Helaman 2 first appeared on The Interpreter Foundation.
PDF feed of Interpreter: A Journal of Latter-day Saint Faith and Scholarship
Abstract: There are many reasons why a narrator may choose to provide or withhold the names of various characters. This article hypothesizes that Mormon intentionally omitted the name of a key character from the book of Helaman related to the origin of the Gaddianton robbers. While it is not possible to know exactly what information […] The post Nameless: Mormon's Dramatic Use of Omission in Helaman 2 first appeared on The Interpreter Foundation.
Abstract: There is no more important message than that of the Atonement and Resurrection of Jesus Christ. It's life-transforming and world-transforming. It is also the most joyous news imaginable. What Jesus did on our behalf leaves us forever in his debt and should put him at the center of our lives. Easter Sunday,” President Russell […] The post Christ is Risen! Truly, He is Risen! first appeared on The Interpreter Foundation.
ePub feed of Interpreter: A Journal of Latter-day Saint Faith and Scholarship
Abstract: There is no more important message than that of the Atonement and Resurrection of Jesus Christ. It's life-transforming and world-transforming. It is also the most joyous news imaginable. What Jesus did on our behalf leaves us forever in his debt and should put him at the center of our lives. Easter Sunday,” President Russell […] The post Christ is Risen! Truly, He is Risen! first appeared on The Interpreter Foundation.
PDF feed of Interpreter: A Journal of Latter-day Saint Faith and Scholarship
Abstract: There is no more important message than that of the Atonement and Resurrection of Jesus Christ. It's life-transforming and world-transforming. It is also the most joyous news imaginable. What Jesus did on our behalf leaves us forever in his debt and should put him at the center of our lives. Easter Sunday,” President Russell […] The post Christ is Risen! Truly, He is Risen! first appeared on The Interpreter Foundation.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.28.551036v1?rss=1 Authors: Torgerson, C., Ahmadi, H., Choupan, J., Fan, C. C., Blosnich, J. R., Herting, M. Abstract: There remains little consensus about the relationship between sex and brain structure, particularly in childhood. Moreover, few pediatric neuroimaging studies have analyzed both sex and gender as variables of interest - many of which included small sample sizes and relied on binary definitions of gender. The current study examined gender diversity with a continuous felt-gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9-11 years-old (N=7693). Then, a statistical model-building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology, including subcortical volume, cortical thickness, gyrification, and white matter microstructure. The model with sex, but not gender diversity, was the best-fitting model in 75% of gray matter regions and 79% of white matter regions examined. The addition of gender to the sex model explained significantly more variance than sex alone with regard to bilateral cerebellum volume, left precentral cortical thickness, as well as gyrification in the right superior frontal gyrus, right parahippocampal gyrus, and several regions in the left parietal lobe. For mean diffusivity in the left uncinate fasciculus, the model with sex, gender, and their interaction captured the most variance. Nonetheless, the magnitude of variance accounted for by sex was small in all cases and felt-gender score was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9-11 years-old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.18.549575v1?rss=1 Authors: Fortunato, C., Bennasar-Vazquez, J., Park, J., Chang, J. C., Miller, L. E., Dudman, J. T., Perich, M. G., Gallego, J. A. Abstract: There is rich variety in the activity of single neurons recorded during behaviour. Yet, these diverse single neuron responses can be well described by relatively few patterns of neural co-modulation. The study of such low-dimensional structure of neural population activity has provided important insights into how the brain generates behaviour. Virtually all of these studies have used linear dimensionality reduction techniques to estimate these population-wide co-modulation patterns, constraining them to a flat "neural manifold". Here, we hypothesised that since neurons have nonlinear responses and make thousands of distributed and recurrent connections that likely amplify such nonlinearities, neural manifolds should be intrinsically nonlinear. Combining neural population recordings from monkey motor cortex, mouse motor cortex, mouse striatum, and human motor cortex, we show that: 1) neural manifolds are intrinsically nonlinear; 2) the degree of their nonlinearity varies across architecturally distinct brain regions; and 3) manifold nonlinearity becomes more evident during complex tasks that require more varied activity patterns. Simulations using recurrent neural network models confirmed the proposed relationship between circuit connectivity and manifold nonlinearity, including the differences across architecturally distinct regions. Thus, neural manifolds underlying the generation of behaviour are inherently nonlinear, and properly accounting for such nonlinearities will be critical as neuroscientists move towards studying numerous brain regions involved in increasingly complex and naturalistic behaviours. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.15.548973v1?rss=1 Authors: Upton, R., Calatayud, N. E., Clulow, S., Brett, D., Burton, A. L., Colyvas, K., Mahony, M., Clulow, J. Abstract: There are strong potential benefits of incorporating assisted reproductive technologies (ARTs) into conservation programs for the management of threatened amphibians as the global amphibian decline continues. As sperm cryopreservation and other ARTs advance in common species, focus on non-lethal sperm collection methods for threatened amphibians is imperative. We aimed to realise this goal by testing various doses of exogenous hormones for non-lethal induction of spermiation in a threatened frog (Litoria aurea) and develop cold storage and cryopreservation protocols following the recovery of urinic sperm. Our major findings include: (1) that sperm release could be induced in high concentrations with 20 IU/g bodyweight of human chorionic gonadotrophin (hCG); (2) high levels ( greater than 50%) of live, motile sperm could be recovered post-cryopreservation by treating the sperm with 15% v/v DMSO and 1% w/v sucrose pre-freeze; and (3) urinic sperm stored at 5{degrees}C retained motility over a 14-day period. Our findings demonstrate that it is possible to obtain and store large quantities of quality sperm from a threatened amphibian via non-lethal means, representing an important step forward for the use of ARTs in conservation programs for rare and threatened species. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.547102v1?rss=1 Authors: Cole, K., Parsons, R. Abstract: There is now ample evidence that the strength and underlying mechanisms of memory formation can be drastically altered by prior experience. However, the prior work using rodent models on this topic has used only males as subjects, and as a result, we do know whether or not the effects of prior experience on subsequent learning are similar in both sexes. As a first step towards addressing this shortcoming rats of both sexes were given auditory fear conditioning, or fear conditioning with unsignaled shocks, followed an hour or a day later by a single pairing of light and shock. Fear memory for each experience was assessed by measuring freezing behavior to the auditory cue and fear-potentiated startle to the light. Results showed that males trained with auditory fear conditioning showed facilitated learning to the subsequent visual fear conditioning session when the two training sessions were separated by one hour or one day. Females showed evidence of facilitation in rats given auditory conditioning when they were spaced by an hour, but not when they were spaced by one day. Contextual fear conditioning did not support the facilitation of subsequent learning under any conditions. These results indicate that the mechanism by which prior fear conditioning facilitates subsequent learning differs between sexes, and they set the stage for mechanistic studies to understand the neurobiological basis of this sex difference. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.26.546352v1?rss=1 Authors: Jiang, Z., An, X., Shuang Liu, S., Yin, E., Yan, Y., Ming, D. Abstract: There are significant intra-individual and inter-individual variabilities in audiovisual temporal perception. Previous studies have shown that prestimulus neural variability could reflect behavioral variabilities. We aimed to investigate whether prestimulus neural variability can predict behavioral variability in audiovisual temporal perception. Furthermore, We also explored whether prestimulus neural variability directly influences behavioral responses or indirectly impacts perceptual decisions through post-stimulus-evoked responses. We analyzed the electroencephalography (EEG) data from a paradigm where the twenty-eight human subjects performed a simultaneity judgment (SJ) task in the beep-flash stimulus. The prestimulus weighted permutation entropy (WPE) was the indicator of neural variability in this study. We found that prestimulus frontal WPE could predict the individual's TBW in auditory- and visual-leading conditions. In addition, increased prestimulus parietal WPE was associated with more asynchronous responses. Prestimulus frontal WPE may be associated with top-down cognitive control, while parietal WPE may be related to bottom-up cortical excitability. Furthermore, poststimulus evoked responses could mediate the relation between prestimulus WPE and the individual's TBW or perceptual responses. These results suggested that prestimulus WPE was a marker in reflecting intra-individual and inter-individual variabilities in audiovisual temporal perception. Significantly, prestimulus WPE might influence perceptual responses by affecting poststimulus sensory representations. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.01.538959v1?rss=1 Authors: Dorsey, S. G., Mocci, E., Lane, M. V., Krueger, B. K. Abstract: There is an increased incidence of autism among the children of women who take the anti-epileptic, mood stabilizing drug, valproic acid (VPA) during pregnancy, moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNAseq data ob-tained from fetal mouse brains 3 hr after VPA administration revealed that VPA significantly [p(FDR) less than or equal to 0.025] increased or decreased the expression of approximately 7,300 genes. No significant sex dif-ferences in VPA-induced gene expression were observed. Expression of genes associated with neurodevelopmental disorders such as autism as well as neurogenesis, axon growth and synapto-genesis, GABAergic, glutaminergic and dopaminergic synaptic transmission, perineuronal nets, and circadian rhythms was dysregulated by VPA. Moreover, expression of 400 autism risk genes was significantly altered by VPA. In addition, expression of 247 genes that have been reported to play fundamental roles in the development of the nervous system, but are not linked to autism by GWAS, was significantly increased or decreased by VPA. The goal of this study was to identify mouse genes that are: (a) significantly up- or down-regulated by VPA in the fetal brain and (b) known to be associated with autism and/or to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity in the postnatal and adult brain. The set of genes meeting these criteria provides potential targets for future hypothesis-driven approaches to elucidating the proximal underlying causes of defective brain connectivity in neuro-developmental disorders such as autism. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.12.536421v1?rss=1 Authors: Alberti, F., Menardi, A., Margulies, D. S., Vallesi, A. Abstract: There is a growing interest in neuroscience for how individual-specific structural and functional features of the cortex relate to cognitive traits. This work builds on previous research which, using classical high-dimensional approaches, has proven that the interindividual variability of functional connectivity profiles reflects differences in fluid intelligence. To provide an additional perspective into this relationship, the present study uses a recent framework for investigating cortical organization: functional gradients. This approach places local connectivity profiles within a common low-dimensional space whose axes are functionally interretable dimensions. Specifically, this study uses a data-driven approach focussing on areas where FC variability is highest across individuals to model different facets of intelligence. For one of these loci, in the right ventral-lateral prefrontal cortex (vlPFC), we describe an association between fluid intelligence and relative functional distance from sensory and high-cognition systems. Furthermore, the topological properties of this region indicate that with decreasing functional affinity with the latter, its functional connections are more evenly distributed across all networks. Participating in multiple functional networks may reflect a better ability to coordinate sensory and high-order cognitive systems. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.14.532686v1?rss=1 Authors: Kim, Y., Joshi, A. A., Choi, S., Joshi, S. H., Bhushan, C., Varadarajan, D., Haldar, J. P., Leahy, R. M., Shattuck, D. W. Abstract: There has been a concerted effort by the neuroimaging community to establish standards for computational methods for data analysis that promote reproducibility and portability. In particular, the Brain Imaging Data Structure (BIDS) specifies a standard for storing imaging data, and the related BIDS App methodology provides a standard for implementing containerized processing environments that include all necessary dependencies to process BIDS datasets using image processing workflows. We present the BrainSuite BIDS App, which encapsulates the core MRI processing functionality of BrainSuite within the BIDS App framework. Specifically, the BrainSuite BIDS App implements a participant-level workflow comprising three pipelines and a corresponding set of group-level analysis workflows for processing the participant-level outputs. The BrainSuite Anatomical Pipeline (BAP) extracts cortical surface models from a T1-weighted (T1w) MRI. It then performs surface-constrained volumetric registration to align the T1w MRI to a labeled anatomical atlas, which is used to delineate anatomical regions of interest in the MRI brain volume and on the cortical surface models. The BrainSuite Diffusion Pipeline (BDP) processes diffusion-weighted imaging (DWI) data, with steps that include coregistering the DWI data to the T1w scan, correcting for geometric image distortion, and fitting diffusion models to the DWI data. The BrainSuite Functional Pipeline (BFP) performs fMRI processing using a combination of FSL, AFNI, and BrainSuite tools. BFP coregisters the fMRI data to the T1w image, then transforms the data to the anatomical atlas space and to the Human Connectome Project's grayordinate space. Each of these outputs can then be processed during group-level analysis. The outputs of BAP and BDP are analyzed using the BrainSuite Statistics in R (bssr) toolbox, which provides functionality for hypothesis testing and statistical modeling. The outputs of BFP can be analyzed using atlas-based or atlas-free statistical methods during group-level processing. These analyses include the application of BrainSync, which synchronizes the time-series data temporally and enables comparison of resting-state or task-based fMRI data across scans. We also present the BrainSuite Dashboard quality control system, which provides a browser-based interface for reviewing the outputs of individual modules of the participant-level pipelines across a study in real-time as they are generated. BrainSuite Dashboard facilitates rapid review of intermediate results, enabling users to identify processing errors and make adjustments to processing parameters if necessary. The comprehensive functionality included in the BrainSuite BIDS App provides a mechanism for rapidly deploying the BrainSuite workflows into new environments to perform large-scale studies. We demonstrate the capabilities of the BrainSuite BIDS App using structural, diffusion, and functional MRI data from the Amsterdam Open MRI Collection's Population Imaging of Psychology dataset. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.14.532617v1?rss=1 Authors: Mah, A., Bossio, V., Constantinople, C. M. Abstract: There are many ways to compute value. For instance, animals can compute value by learning from the past or by imagining future outcomes, but it is unclear if or how these computations interact. We used high-throughput training to collect statistically powerful datasets from 240 rats performing a temporal wagering task with hidden reward states. Rats adjusted how quickly they initiated trials and how long they waited for rewards across states, balancing effort and time costs against expected rewards. Statistical modeling revealed that animals computed the value of the environment differently when initiating trials versus when deciding how long to wait for rewards, even though these decisions were only seconds apart. This work reveals that sequential decisions use parallel value computations on single trials. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.21.529079v1?rss=1 Authors: Gort Vicente, J. Abstract: There is growing evidence that many forms of neural computation may be implemented by low dimensional dynamics unfolding at the population scale. However, neither the connectivity structure nor the general capabilities of these embedded dynamical processes are currently understood. In this work, the two most common formalisms of firing-rate models are evaluated using tools from analysis, topology and nonlinear dynamics in order to provide plausible explanations for these problems. It is shown that low-rank structured connectivity predicts the formation of invariant and globally attracting manifolds in both formalisms, which generalizes existing theories to different neural models. Regarding the dynamics arising in these manifolds, it is proved they are topologically equivalent across the considered formalisms. It is also stated that under the low-rank hypothesis, dynamics emerging in neural models are universal. These include input-driven systems, which broadens previous findings. It is then explored how low-dimensional orbits can bear the production of continuous sets of muscular trajectories, the implementation of central pattern generators and the storage of memory states. It is also proved these dynamics can robustly simulate any Turing machine over arbitrary bounded memory strings, virtually endowing rate models with the power of universal computation. In addition, it is shown how the low-rank hypothesis predicts the parsimonious correlation structure observed in cortical activity. Finally, it is discussed how this theory could provide a useful tool from which to study neuropsychological phenomena using mathematical methods. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.19.529148v1?rss=1 Authors: Kock, R. M. D., Ghosh, A. Abstract: There is considerable trial-to-trial variability in single cortical neurons when performing the same action repeatedly. One possibility is that neural populations are more stable in representing actions; alternatively, they too may be distinctly engaged from trial-to-trial. To address the nature of variability in large neural populations, we captured the EEG signals time-locked to repeated voluntary thumb flexion movements (~500 repetitions, 23 subjects). By using non-negative matrix factorization on the low-frequency sensorimotor cortical signals, we quantified the trial-to-trial motor-related potentials (MRPs) in terms of prototypical signals (meta-MRPs) and their corresponding prominence at each trial (meta-trials). Clustering the meta-MRPs across the sampled population revealed 5 distinct signal patterns. There were brain-wide correlates of these meta-MRP clusters. Cortical hemispheres were distinctly recruited from trial-to-trial as certain clusters were accompanied by bilateral motor negativity while others were characterized by ipsilateral motor negativity. The sensory feedback too was distinctly processed from trial-to-trial as the central post-movement positivity was present only for certain clusters. A poorly understood pre-motor positivity accompanied all clusters albeit varying in their timing from trial-to-trial. These patterns - including the time-varying positivity preceding the movement - were rendered invisible by the traditional averaging of the signals. We suggest that the variability in EEG signals is not just noise but a consequence of distinct activation patterns deployed by the cortex. We support the idea that the cortex flexibly switches between distinct forms of neural processing to achieve the same behavioral goals. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.19.528206v1?rss=1 Authors: Chapelet, G., Beguin, N., Castellano, B., Grit, I., Oullier, T., Neunlist, M., Blottiere, H., Rolli-Derkinderen, M., Le Drean, G., Derkinderen, P. Abstract: There is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson's disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alpha-synuclein, a presynaptic neuronal protein genetically and neuropathologically linked to PD came to reinforce the assumption that EEC might be a key component of the neural circuit between the gut lumen and the brain for the bottom-up propagation of PD pathology. Besides alpha-synuclein, tau is another key protein involved in neurodegeneration and converging evidences indicate that there is an interplay between these two proteins at both molecular and pathological levels. There are no existing studies on tau in EEC and therefore we set out to examine the isoform profile and phosphorylation state of tau in these cells. Methods Surgical specimens of human colon from control subjects were analyzed by immunohistochemistry using a panel of anti-tau antibodies together with chromogranin A and Glucagon-like peptide-1 (two EEC markers) antibodies. To investigate tau phosphorylation and expression further, two EEC lines, namely GLUTag and NCI-H716 were analyzed by western blot after dephosphorylation with pan-tau and tau isoform specific antibodies. Eventually, GLUTag were treated with propionate and butyrate, two short chain fatty acids known to sense EEC, and analyzed at different time points by western blot with an antibody specific for tau phosphorylated at Thr205. Results We found that tau is expressed and phosphorylated in EEC in adult human colon and that both EEC lines mainly express two tau isoforms that are phosphorylated under basal condition. Both propionate and butyrate regulated tau phosphorylation state by decreasing its phosphorylation at Thr205. Conclusion and inference Our study is the first to characterize tau in human EEC and in EEC lines. As a whole, our findings provide a basis to unravel the functions of tau in EEC and to further investigate the possibility of pathological changes in tauopathies and synucleinopathies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.09.527783v1?rss=1 Authors: Kwak, S., Lee, D., Jang, S., Kim, S., Kim, S., Doo, W., Kwak, E. Abstract: There has been no study on the relationship between chronic tinnitus and harmonic templates. Harmonic templates are harmonically structured receptive fields in the auditory system in which all frequency components are integer multiples of a common fundamental frequency (F0). In this study, data from 19 harmonic templates from each of 196 chronic tinnitus patients were analyzed and mathematical modeling was performed to quantify the loudness of chronic tinnitus. High-resolution hearing threshold data were obtained by algorithmic pure tone audiometry (PTA) conducting automated PTA at 134 frequency bands with 1/24 octave resolution from 250 Hz to 12,000 Hz. The result showed that there is an intriguing relationship between the auditory instability of harmonic templates and simplified tinnitus severity score (STSS). This study provides several mathematical models to estimate tinnitus severity and the precise quantification of the loudness of chronic tinnitus. Our computational models and analysis of the behavioral hearing threshold fine structure suggest that the cause of severe chronic tinnitus could be a severe disparity between different temporal capacities of each neural oscillator in a certain harmonic template. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
ePub feed of Interpreter: A Journal of Latter-day Saint Faith and Scholarship
Review of Cheryl L. Bruno, Joe Steve Swick III, and Nicholas S. Literski, Method Infinite: Freemasonry and the Mormon Restoration (Salt Lake City: Greg Kofford Books, 2022). 544 pages. $44.95 (hardback); $34.95 (softcover). Abstract: There is much to celebrate in this important new study of Freemasonry and the Latter-day Saints. To their credit, the authors have succeeded […] The post An Important New Study of Freemasonry and the Latter-day Saints: What's Good, What's Questionable, and What's Missing in Method Infinite first appeared on The Interpreter Foundation.
PDF feed of Interpreter: A Journal of Latter-day Saint Faith and Scholarship
Review of Cheryl L. Bruno, Joe Steve Swick III, and Nicholas S. Literski, Method Infinite: Freemasonry and the Mormon Restoration (Salt Lake City: Greg Kofford Books, 2022). 544 pages. $44.95 (hardback); $34.95 (softcover). Abstract: There is much to celebrate in this important new study of Freemasonry and the Latter-day Saints. To their credit, the authors have succeeded […] The post An Important New Study of Freemasonry and the Latter-day Saints: What's Good, What's Questionable, and What's Missing in Method Infinite first appeared on The Interpreter Foundation.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.09.523285v1?rss=1 Authors: O'Neill, G. C., Mellor, S., Seymour, R. A., Alexander, N., Tierney, T. M., Timms, R. C., Maguire, E. A., Barnes, G. R. Abstract: There is renewed interest in electrical activity that extends beyond the typical electrophysiological 100 Hz bandwidth. This activity, often in the anterior temporal lobe, has been attributed to processes ranging from memory consolidation to epileptiform activity. Here, using an open-access resting state magnetoencephalography (MEG) dataset (n = 89), and a second task-based MEG dataset, we could reliably localise high-frequency power to the temporal lobes across multiple bands up to 300-400 Hz. A functional connectivity analysis of this activity revealed a robust resting state bilateral network between the temporal lobes. However, we also found robust coherence in the 100-200 and 200-300 Hz bands between source reconstructed MEG data and the electrooculography (EOG) localised to within the temporal poles. Additional denoising schemes applied to the data could reduce power localisation to the temporal poles but the topography of the functional network did not drastically alter. Whilst it is clear that this network is biological and robust to established denoising methods, we cannot definitively rule yet on whether this is of neural or myogenic origin. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.25.517978v1?rss=1 Authors: Shen, B. Q., Sankaranarayanan, I., Price, T. J., Tavares-Ferreira, D. Abstract: There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data in a sex-aware fashion. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data in a sex-aware fashion. Interestingly, 14 out of 15 preclinical studies and 4 out of 5 clinical studies that analyzed data in a sex-aware fashion have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex-awareness in data analysis. The preclinical literature identifies a sex difference in prostaglandin D2 synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and sex-aware analysis in data analysis in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514442v1?rss=1 Authors: Lazaris, A., Metrakos, P., Petrillo, S. Abstract: There are a number of methods for the isolation of extracellular vesicles (EV) which include the traditional ultracentrifugation to column-based kits available from different companies. Isolation of EVs from complex fluids, such as blood, has several challenges as the detection of low abundance molecules can easily be masked by more abundant proteins, when performing mass spectrometry. For this reason, several commercially available kits contain Thromboplastin D (TP-D) to promote clotting, thus removing clotting factors and abundant proteins resulting in increased detection of proteins. Our study demonstrates that plasma pretreated with Rabbit brain derived TP-D (the most common additive), generated a dynamic range of proteins compared to plasma alone, however, most of these proteins were contaminants introduced from the TP-D (99.1% purity). As an alternative, we tested recombinant TP and demonstrated that although it did not introduce any significant contaminants, we did not see any difference in the detection of proteins. Thus TP-D is not required, and any protein additives must be carefully screened. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.28.514058v1?rss=1 Authors: Symeonidou, E.-R., Ferris, D. Abstract: There is a need to develop appropriate balance training interventions to minimize the risk of falls. Recently, we found that intermittent visual occlusions can substantially improve the effectiveness and retention of balance beam walking practice (Symeonidou and Ferris 2022). We sought to determine how the intermittent visual occlusions affect electrocortical activity during beam walking. We hypothesized that areas involved in sensorimotor processing and balance control would demonstrate spectral power changes and inter-trial coherence modulations after loss and restoration of vision. Ten healthy young adults practiced walking on a treadmill-mounted balance beam while wearing high-density EEG and experiencing reoccurring visual occlusions. Results revealed spectral power fluctuations and inter-trial coherence changes in the visual, occipital, temporal, and sensorimotor cortex as well as the posterior parietal cortex and the anterior cingulate. We observed a prolonged alpha increase in the occipital, temporal, sensorimotor, and posterior parietal cortex after the occlusion onset. In contrast, the anterior cingulate showed a strong alpha and theta increase after the occlusion offset. We observed transient phase synchrony in the alpha, theta, and beta bands within the sensory, posterior parietal, and anterior cingulate cortices immediately after occlusion onset and offset. Our results provide support for cross-modal phase resetting and enhanced processing in areas involved in sensory processing and balance control as an explanation for increased long-term balance improvement when training with intermittent visual occlusions. Our training intervention could be implemented in senior and rehabilitation centers, improving the quality of life of elderly and neurologically impaired individuals. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.19.512820v1?rss=1 Authors: Soo, W. W. M., Lengyel, M. Abstract: There continues to be a trade-off between the biological realism and performance of neural networks. Contemporary deep learning techniques allow neural networks to be trained to perform challenging computations at (near) human-level, but these networks typically violate key biological constraints. More detailed models of biological neural networks can incorporate many of these constraints but typically suffer from subpar performance and trainability. Here, we narrow this gap by developing an effective method for training a canonical model of cortical neural circuits, the stabilized supralinear network (SSN), that in previous work had to be constructed manually or trained with undue constraints. SSNs are particularly challenging to train for the same reasons that make them biologically realistic: they are characterized by strongly-connected excitatory cells and expansive firing rate non-linearities that together make them prone to dynamical instabilities unless stabilized by appropriately tuned recurrent inhibition. Our method avoids such instabilities by initializing a small network and gradually increasing network size via the dynamics-neutral addition of neurons during training. We first show how SSNs can be trained to perform typical machine learning tasks by training an SSN on MNIST classification. We then demonstrate the effectiveness of our method by training an SSN on the challenging task of performing amortized Markov chain Monte Carlo-based inference under a Gaussian scale mixture generative model of natural image patches with a rich and diverse set of basis functions - something that was not possible with previous methods. These results open the way to training realistic cortical-like neural networks on challenging tasks at scale. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.19.510727v1?rss=1 Authors: Lin, C.-H. S., Tierney, T. M., Mellor, S., ONeill, G. C., Bestmann, S., Barnes, G. R., Miall, R. C. Abstract: There is a profound lack of electrophysiological data from the cerebellum in humans, as compared to animals, because the pervading perception is that it is difficult to record human cerebellar activity non-invasively using MEG or EEG. We used on-scalp magnetoencephalography based on optically pumped magnetometers to detect learning related cerebellar signals in a classical eyeblink conditioning paradigm. In four healthy human adults, we observed unconditioned stimulus-related evoked responses locating in the cerebellum. These evoked responses diminished during the acquisition of conditioned responses, which corresponds with previous observed changes of Purkinje cell activities in animals. We also observed evoked responses immediately before conditioned blinks in 3 out of 4 participants, which were also located in the cerebellum. We discuss the potential nature of these cerebellar evoked responses and future applications of OP-MEG to the studies of human cerebellar physiology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.12.511820v1?rss=1 Authors: Tullo, S., Miranda, A. S., del Cid-Pellitero, E., Peng Lim, M., Gallino, D., Attaran, A., Patel, R., Novikov, V., Park, M., Beraldo, F., Luo, W., Shlaifer, I., Durcan, T. M., Bussey, T. J., Saksida, L. M., Fon, E. A., Prado, V. F., Prado, M. A. M., Chakravarty, M. M. Abstract: There is significant evidence suggesting aggregated misfolded alpha-synuclein, a major component of Lewy bodies, propagates in a prion-like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. Animal models are essential for understanding and developing treatments for these diseases. However, despite modelling human pathology, most endpoints studied in mice do not translate to humans. Furthermore, the progression by which alpha-synuclein misfolding affects human-relevant measures such as brain volume and underlying subtle, high-level cognitive deficits is poorly understood. Here we used a mouse model of synucleinopathy; hemizygous M83 human A53T alpha-synuclein transgenic mice inoculated with recombinant human alpha-synuclein preformed fibrils (PFF) injected in the right striatum to initiate alpha-synuclein misfolding and aggregation. We examined alpha-synuclein-induced atrophy at 90 days post-injection using ex vivo magnetic resonance imaging as well as high-level cognition and motor function, as biomarkers of alpha-synuclein toxicity. We observed widespread atrophy in bilateral regions that project to or receive input from the injection site, highlighting a network of regions that are consistent with structural changes observed in humans with PD. Moreover, we detected early deficits in reversal learning with touchscreen testing in PFF-injected mice prior to motor dysfunction, consistent with the pathology observed in cortical-striatal and thalamic loops. We show, using translational approaches in mice, that progression of prion-like spreading of alpha-synuclein causes selective atrophy via connected brain regions leading to high-level cognitive deficits. We propose that precise imaging and cognitive biomarkers can provide a more direct and human-relevant measurement of alpha-synuclein-induced toxicity in pre-clinical testing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.12.511938v1?rss=1 Authors: Yang, C. C., Totzek, J. F., Lepage, M., Lavigne, K. M. Abstract: There is robust evidence for sex differences in domain-specific cognitive performance in the general population, where females typically show an advantage for verbal memory (VM), while males tend to perform better on tasks of spatial memory (SM). Sex differences in brain structure and connectivity are also well-documented and may provide insight into sex differences in cognition. In this study, we examined sex differences in cognition and morphometric brain connectivity of a large healthy sample (N = 31,180) from the UK Biobank dataset. Using T1-weighted magnetic resonance imaging (MRI) scans and regional cortical thickness values, we applied jackknife bias estimation and graph theory to obtain subject-specific measures of morphometric brain connectivity, hypothesizing that sex-related differences in brain network global efficiency, or overall connectivity, would underlie observed cognitive differences. As predicted, females demonstrated better VM performance and males showed an advantage in SM. Females also demonstrated faster processing speed, with no observed sex difference in executive functioning. Males tended to have higher global efficiency, as well as higher regional connectivity (nodal strengths) in both the left and right hemispheres relative to females. Furthermore, higher global efficiency in males was found to mediate observed sex differences in cognition, predicting poorer verbal memory performance, better spatial memory, and slower processing speed in males. These findings contribute to an improved understanding of the way biological sex and differences in cognitive performance are related to morphometric brain connectivity as derived from graph-theoretic methods. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.29.510105v1?rss=1 Authors: Heiland, M., Connolly, N. M. C., Nguyen, N. T., Kesavan, J. C., Fanning, K., Sanfeliu, A., Yan, Y., Veno, M. T., Costard, L. S., Neubert, V., Hill, T. D. M., Rosenow, F., Bauer, S., Kjems, J., Morris, G., Henshall, D. Abstract: There remains an urgent need for new therapies for drug-resistant epilepsy (DRE). Sodium channel blockers are effective for seizure control in common forms of epilepsy, but loss of sodium channel function underlies some genetic forms of epilepsy. Approaches that provide bi-directional control of sodium channel expression are needed. MicroRNAs (miRNA) are small non-coding RNAs which negatively regulate gene expression. Here, we show that genome-wide miRNA screening of hippocampal tissue from a rat epilepsy model, mice treated with the novel anti-seizure medicine cannabidiol (CBD) and plasma from patients with DRE, converge on a single target, miR-335-5p. Pathway analysis on predicted and validated miR-335-5p targets identified multiple voltage-gated sodium channels (VGSCs). Intracerebroventricular injection of antisense oligonucleotides against miR-335-5p resulted in upregulation of Scn1a, Scn2a and Scn3a in the mouse brain and an increased action potential rising phase and greater excitability of hippocampal pyramidal neurons in brain slice recordings, consistent with VGSCs as functional targets of miR-335-5p. Blocking of miR-335-5p also increased voltage-gated sodium currents in human iPSC-derived neurons. Inhibition of miR-335-5p increased susceptibility to tonic-clonic seizures in the pentylenetetrazole seizure model, whereas AAV9-mediated overexpression of miR-335-5p reduced seizure severity and improved survival. These studies suggest modulation of miR-335-5p may be a means to regulate VGSCs and affect brain excitability and seizures. Changes to miR-335-5p may reflect compensatory mechanisms to control excitability and could provide new biomarker or therapeutic strategies for different types of drug-resistant epilepsy. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.20.508721v1?rss=1 Authors: Poyo Solanas, M., Zhan, M., de Gelder, B. Abstract: There is substantial evidence about affective stimulus processing outside awareness in healthy participants and brain-damaged patients. However, there are still methodological concerns mainly relating to the methods used to assess awareness. In two experiments, we investigated the processing of social threat in healthy participants by combining the continuous flash suppression paradigm and the perceptual awareness scale, a finer measure of perceptual awareness than dichotomous (seen/unseen) responses. Our behavioral results show a gradual relationship between emotional recognition and perceptual awareness. Recognition sensitivity was also higher for fearful than angry bodies for all visual awareness levels except for the perceptual unawareness condition where performance was at chance level. Interestingly, angry body expressions were suppressed for a shorter duration than neutral and fearful ones. Pupil dilation was a function of affective expression, the duration of suppression and the level of perceptual awareness. In conclusion, behavioral as well as pupillary responses showed a gradual relationship with perceptual awareness, and this relationship was influenced by the specific stimulus category. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.06.506787v1?rss=1 Authors: Mobarak-Abadi, M., Mahmoudi-Aznave, A., Dehghani, H., Zarei, M., Vahdat, S., Doyon, J., Khatibi, A. Abstract: There are unique challenges in the preprocessing of spinal cord fMRI data, particularly voluntary or involuntary movement artifacts during image acquisition. Despite advances in data processing techniques for movement detection and correction, there are challenges in extrapolating motion correction algorithm developments in the brain cortex to the brainstem and spinal cord. We trained a Deep Learning-based convolutional neural network (CNN) via an unsupervised learning algorithm, called DeepRetroMoCo, to detect and correct motions in axial T2*-weighted spinal cord data. Spinal cord fMRI data from 27 participants were used for training of the network (135 runs for training and 81 runs for testing). We used average temporal signal-to-noise-ratio (tSNR) and Delta Variation Signal (DVARS) of raw and motion-corrected images to compare the outcome of DeepRetroMoco with sct_fmri_moco implemented in the spinal cord toolbox. The average tSNR in the cervical cord was significantly higher when DeepRetroMoco was used for motion correction compared to sct_fmri_moco method. Average DVARS was lower in images corrected by DeepRetroMoco than those corrected by sct_fmri_moco. The average processing time for DeepRetroMoco was also significantly shorter than sct_fmri_moco. Our results suggest that DeepRetroMoCo improves motion correction procedures in fMRI data acquired from the cervical spinal cord. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.02.506424v1?rss=1 Authors: Xiu, B., Paul, B. T., Chen, J. M., Le, T. N., Lin, V. Y., Dimitrijevic, A. Abstract: There is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and "real-world" listening environments and stimuli. Speech sounds in the real world are often accompanied by visual cues, background environmental noise and is generally in the context of a connected conversation. The aims of this study were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high density EEG while CI users listened/watched a naturalistic stimulus (i.e., the television show, "The Office"). We used continuous EEG to quantify "speech neural tracking" (i.e., TRFs, temporal response functions) to the television show audio track and additionally 8-12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show mimicking a natural noisy environment. The task included an additional condition of audio-only (no video). After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they could understand. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). The addition of the background noise reduced the degree of speech neural tracking. Mixed effect modeling showed that listening demand and conversation understanding were correlated to cortical speech tracking such that high demand and low conversation understanding lower associated with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power such that higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between speech perception and quality of life in CI users. However, the physiological responses to complex natural speech may anticipate aspects of quality-of-life measures such as self-perceived listening demand. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Summary of the article titled A place-based model for understanding community resilience to natural disasters from 2008 by Susan Cutter, Lindsey Barnes, Melissa Berry, Christopher Burton, Elijah Evans, Eric Tate, and Jennifer Webb, published in the Global Environmental Change journal. Since we are investigating the future of cities, I thought it would be interesting to see a framework for disaster resilience of place model. This article investigates and proposes a comparative assessment for disaster resilience at the local or community level with a set of variables for easier implementation. You can find the article through this link. Abstract: There is considerable research interest on the meaning and measurement of resilience from a variety of research perspectives including those from the hazards/disasters and global change communities. The identification of standards and metrics for measuring disaster resilience is one of the challenges faced by local, state, and federal agencies, especially in the United States. This paper provides a new framework, the disaster resilience of place (DROP) model, designed to improve comparative assessments of disaster resilience at the local or community level. A candidate set of variables for implementing the model are also presented as a first step towards its implementation. You can find the transcript through this link. What wast the most interesting part for you? What questions did arise for you? Let me know on twitter @WTF4Cities! I hope this was an interesting episode for you and thanks for tuning in. Music by Lesfm from Pixabay
Abstract: There are many ways to covertly obtain access to user accounts, including: week passwords, accounts still valid after a user leaves the enterprise, dormant or lingering test accounts, shared accounts that have not been changed in months or years, service accounts embedded in applications for scripts, a user having the same password as one they used for an online account. Learn how CIS Control 5 can mitigate some of the most common ways credentials are compromised.Sponsor: Keeper Security interview with Marcia Dempster, Sr. Director of Channel Sales at minute 48:21. Learn more here: https://www.keepersecurity.com/Marcia Dempster: https://www.linkedin.com/in/marcia-dempster-03280914/Sponsor: CIS CIS-CAT (https://learn.cisecurity.org/cis-cat-lite)Co-hosts:Ryan Weeks: https://www.linkedin.com/in/ryanweeks/Phyllis Lee: https://www.linkedin.com/in/phyllis-lee-21b58a1a4/Wes Spencer: https://www.linkedin.com/in/wesspencer/
Abstract: There is a cybersecurity saying; “you can't protect what you don't know about.” Without visibility into your information assets, their value, where they live, how they relate to each other and who has access to them, any strategy for protection would be inherently incomplete and ineffective.Note sponsors are at the end at minute 28:30 The Why might an MSP want to listen? Most MSPs only capture 50% of the assets on a client's network.Min 2:30 - 8:46 (Ryan Weeks, CISO of Datto discusses)Importance of asset management.What defines an asset.What defines good asset management.What are common assets missed in an MSPs inventory.Min 8:47 - 16:06 (Wes Spencer, CISO of Perch Security)The repercussions of poor asset management.Importance of Asset Management, as it pertains to Incident Response.How asset management help with IR plans & Tabletops.Min 16:08 - 23:05 (Brian Blakely, Fractional CISO of Cosant Cybersecurity)What your policy statement should include.Learn the importance of Data Flow Diagrams (DFDs).Control objectives and standards MSPs need to consider.Asset considerations on the Right & Left side of "Boom".Min 23:06 - 28:30 (Phyllis Lee, Sr. Director of Controls for CIS)Why CIS and most frameworks start with asset management.The progression of sub-controls as an organization moves from IG1 - IG3 in CIS.What actionable steps should MSPs take to successfully implement Control 1 & 2.Sponsors:Center for Internet Security: Phyllis Lee (28:30 - 30:58)CSAT Pro - learn more here: https://www.cisecurity.org/cybersecurity-tools/cis-cat-pro/Netalytics Security:Shiva Shankar (31:00 - 38:50)CyberCNS: https://www.cybercns.com/
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.22.393355v1?rss=1 Authors: Tran, T. T., Tobin, K. E., Block, S. H., Puliyadi, V., Gallagher, M., Bakker, A. Abstract: There has been considerable focus on investigating age-related memory changes in cognitively healthy older adults, in the absence of neurodegenerative disorders. Previous studies have reported age-related domain-specific changes in older adults, showing increased difficulty encoding and processing object information but minimal to no impairment in processing spatial information compared to younger adults. However, few of these studies have examined age-related changes in the encoding of concurrently presented object and spatial stimuli, specifically the integration of both spatial and non-spatial (object) information. To more closely resemble real-life memory encoding and the integration of both spatial and non-spatial information, the current study developed a new experimental paradigm with novel environments that allowed for the placement of different objects in different positions within the environment. The current findings show that older adults have decreased performance in recognizing changes of the object position within the spatial context but no significant differences in recognizing changes in the identity of the object within the spatial context compared to younger adults. These findings suggest there may be potential age-related differences in the mechanisms underlying the representations of complex environments and furthermore, the integration of spatial and non-spatial information may be differentially processed relative to independent and isolated representations of object and spatial information. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.10.377523v1?rss=1 Authors: Smagin, D. A., Babenko, V. N., Kovalenko, I. L., Galyamina, A. G., Redina, O. E., Kudryavtseva, N. N. Abstract: There are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.10.330183v1?rss=1 Authors: He, S., Schein, A., Sarsani, V., Flaherty, P. Abstract: There are distinguishing features or "hallmarks" of cancer that are found across tumors, individuals, and types of cancer, and these hallmarks can be driven by specific genetic mutations. Yet, within a single tumor there is often extensive genetic heterogeneity as evidenced by single-cell and bulk DNA sequencing data. The goal of this work is to jointly infer the underlying genotypes of tumor subpopulations and the distribution of those subpopulations in individual tumors by integrating single-cell and bulk sequencing data. Understanding the genetic composition of the tumor at the time of treatment is important in the personalized design of targeted therapeutic combinations and monitoring for possible recurrence after treatment. We propose a hierarchical Dirichlet process mixture model that incorporates the correlation structure induced by a structured sampling arrangement and we show that this model improves the quality of inference. We develop a representation of the hierarchical Dirichlet process prior as a Gamma-Poisson hierarchy and we use this representation to derive a fast Gibbs sampling inference algorithm using the augment-and-marginalize method. Experiments with simulation data show that our model outperforms standard numerical and statistical methods for decomposing admixed count data. Analyses of real acute lymphoblastic leukemia cancer sequencing dataset shows that our model improves upon state-of-the-art bioinformatic methods. An interpretation of the results of our model on this real dataset reveals co-mutated loci across samples. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.26.355529v1?rss=1 Authors: Makovac, E., Venezia, A., Hohenschurz-Schmidt, D., Dipasquale, O., Jackson, J. B., Medina, S., O'Daly, O., Williams, S. C., McMahon, S. B., Howard, M. A. Abstract: There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. 30 participants underwent Conditioned Pain Modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between 'pressure-only' and 'pressure+cold' stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain, were acquired. Heart Rate Variability (HRV) was simultaneously recorded. Low frequency HRV (LF-HRV) and the CPM score were negatively correlated; individuals with higher LF-HRV during pain reported reductions in pain during CPM. PAG-frontal medial cortex (FMC) and PAG-rostral ventro-medial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-FMC functional connectivity mediated the strength of HRV-CPM association. CPM response magnitude was also negatively associated with PAG and positively associated with FMC grey matter volumes. Our multi-modal approach, using behavioral, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.352559v1?rss=1 Authors: Klinkenberg, I. A. G., Dobel, C., Broeckelmann, A.-K., Plessow, F., Kirschbaum, C., Zwitserlood, P., Junghoefer, M. Abstract: There is growing evidence that humans use olfactory chemosensory signals for social communication, but their role in affective associative learning is largely unknown. To examine this, women implicitly learned face-odor associations by pairing different neutral male faces with either a male chemosignal presumably involved in human mating behavior (dissolved Androstadienone, "AND"), a pleasant smell (dissolved vanillin) or the neutral solvent alone. After learning, women rated faces previously paired with AND or vanillin as more attractive than faces paired with solvent, even though they were unable to identify the contingency of face-odor pairings above chance level. On a neurophysiological level, both AND- and vanillin-associated faces evoked stronger magnetoencephalographic correlates of enhanced emotional attention than solvent-associated faces at early (
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.25.353888v1?rss=1 Authors: Takado, Y., Takuwa, H., Sampei, K., Urushihata, T., Takahashi, M., Shimojo, M., Uchida, S., Nitta, N., Shibata, S., Nagashima, K., Ochi, Y., Ono, M., Maeda, J., Tomita, Y., Sahara, N., Near, J., Aoki, I., Shibata, K., Higuchi, M. Abstract: There is growing interest in the use of magnetic resonance spectroscopy (MRS) to relate brain functions with the concentrations of glutamate (Glu; chief excitatory neurotransmitter) and gamma-aminobutyric acid (GABA; chief inhibitory neurotransmitter) in specific regions. However, it remains unclear how robustly MRS-measured Glu and GABA reflect activities of excitatory and inhibitory neurons, respectively. To address this issue, we conducted MRS measurements of Glu and GABA along with large field-of-view, two-photon mesoscopic imaging of calcium signals in excitatory and inhibitory neurons in the same brain region of living, unanesthetized mice. For monitoring stimulus-driven activations of a brain region, MRS signals and mesoscopic neural activities were measured during two consecutive sessions of 15-min prolonged sensory stimulations. In the first session, activities of putative excitatory neurons were increased, while activities of inhibitory neurons remained at the baseline level. In the second half, while activities of excitatory neurons remained elevated, activities of inhibitory neurons were significantly enhanced. Correspondingly, the concentration of Glu increased without changes in GABA levels in the first MRS session, and the GABA concentration markedly increased from the baseline in the second session. We also assessed regional neurochemical and functional statuses related to spontaneous neural firing by measuring MRS signals and neuronal activities in a mouse model of Dravet syndrome under a resting condition without any task and stimuli. Mesoscopic assessments showed that activities of inhibitory neurons in the cortex were diminished relative to wild-type mice in contrast to spared activities of excitatory neurons. Consistent with these observations, the Dravet model exhibited lower concentrations of GABA than wild-type controls. Collectively, the current investigations demonstrate that the MRS-measured Glu and GABA can reflect spontaneous and stimulated activities of neurons producing and releasing these neurotransmitters in an awake condition. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.16.341834v1?rss=1 Authors: Erfanian, M., Mitchell, A., Aletta, F., Kang, J. Abstract: There is a great deal of literature on contributing environmental factors of soundscape, the perception of the acoustic environment by humans in context. Yet the impact of some contextual and person-related factors is largely unknown. From the questionnaire, adapted from ISO12913-2 and the WHO-5 well-being index, three questions arose: are there differences in Pleasantness and Eventfulness of soundscape among different acoustic environments; are high levels of psychological well-being associated with increased Pleasantness and Eventfulness ratings; and is soundscape Pleasantness and Eventfulness consistent among different age and gender groups? The sample comprised 1180 individual questionnaires, 621 females (52.6%), 532 males (45.1%), mean age 34.95 years, SD= 15.62, collected from eleven urban locations. Hierarchical clustering analysis was done on the mean of each sound source question for each survey location resulting in three clusters of locations based on sound source composition: Natural-dominant, Traffic-dominant and Mixed-sources. A Kruskal-Wallis was conducted to compare the mean Pleasantness and Eventfulness scores of the three clusters, demonstrating that the soundscape assessment was significantly different depending on sound source composition. Multiple linear regression models were used to analyse the relationship between psychological well-being, age, and gender with soundscape Pleasantness and Eventfulness. Our results indicated first that the positive psychological state was associated with Pleasantness in the all-locations and mixed-sources clusters, and with Eventfulness in the traffic-dominant cluster. Secondly, while age was linked to Pleasantness in all clusters it was merely associated with the Eventfulness in the all-locations cluster. Lastly, gender was associated with Pleasantness only in the all-locations cluster. These findings offer empirical grounds for developing theories of the contextual factors on soundscape. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.09.333625v1?rss=1 Authors: Rinkus, R. Abstract: There is increasing realization in neuroscience that information is represented in the brain, e.g., neocortex, hippocampus, in the form sparse distributed codes (SDCs), a kind of cell assembly. Two essential questions are: a) how are such codes formed on the basis of single trials, and how is similarity preserved during learning, i.e., how do more similar inputs get mapped to more similar SDCs. I describe a novel Modular Sparse Distributed Code (MSDC) that provides simple, neurally plausible answers to both questions. An MSDC coding field (CF) consists of Q WTA competitive modules (CMs), each comprised of K binary units (analogs of principal cells). The modular nature of the CF makes possible a single-trial, unsupervised learning algorithm that approximately preserves similarity and crucially, runs in fixed time, i.e., the number of steps needed to store an item remains constant as the number of stored items grows. Further, once items are stored as MSDCs in superposition and such that their intersection structure reflects input similarity, both fixed time best-match retrieval and fixed time belief update (updating the probabilities of all stored items) also become possible. The algorithm's core principle is simply to add noise into the process of choosing a code, i.e., choosing a winner in each CM, which is proportional to the novelty of the input. This causes the expected intersection of the code for an input, X, with the code of each previously stored input, Y, to be proportional to the similarity of X and Y. Results demonstrating these capabilities for spatial patterns are given in the appendix. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.02.322917v1?rss=1 Authors: Green, A. J., Mohlenkamp, M. J., Das, J., Chaudhari, M., Truong, L., Tanguay, R. L., Reif, D. M. Abstract: There are currently 85,000 chemicals registered with the EPA under the Toxic Substances Control Act, but only a small fraction (~5%) have any measured toxicological data. To address this data gap, high-throughput screening (HTS) methods are vital. As part of one such HTS effort, embryonic zebrafish were used to examine a suite of morphological and mortality endpoints at six concentrations from over 1,000 unique chemicals found in the ToxCast library (phase 1 and 2). We hypothesized that by using a conditional Generative Adversarial Network (cGAN) and leveraging this large set of toxicity data, plus chemical structure information, we could efficiently predict toxic outcomes of untested chemicals. CAS numbers for each chemical were used to generate textual files containing three-dimensional structural information for each chemical in the Protein Data Bank (PDB) file format. Utilizing a novel method in this space, we converted the 3D structural information into a weighted set of points while retaining all information about the structure. The in vivo toxicity and chemical data were used to train two neural network generators. The first used regression to train a generator (Go-ZT) to produce toxicity data while the second utilized cGAN architecture to train a generator (GAN-ZT). Our results showed that both Go-ZT and GAN-ZT models produce similar results, but the cGAN achieved higher sensitivity (SE) value of 85.7% vs 71.4%. Conversely, Go-ZT attained a higher specificity (SP), positive predictive value (PPV), and Kappa results of 67.3%, 23.4%, and 0.21 compared to 24.5%, 14.0%, and 0.03 for the cGAN, respectively. By combining both Go-ZT and GAN-ZT, our consensus model improved the SP, PPV, and Kappa, to 75.5%, 25.0%, and 0.211, respectively, resulting in an area under the receiver operating characteristic (AUROC) of 0.663. Considering their potential use as efficient prescreening tools, these new models can provide in vivo toxicity predictions and insight into as-yet untested areas of chemical space to prioritize compounds for HT testing. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.21.306084v1?rss=1 Authors: Feldmann, M., Guo, T., Miller, S. P., Knirsch, W., Kottke, R., Hagmann, C., Latal, B., Jakab, A. Abstract: There is emerging evidence for delayed brain development in neonates with congenital heart disease (CHD). We hypothesize that the perioperative development of the structural brain connectome is a proxy to such delays. Therefore, we set out to quantify the alterations and longitudinal pre- to postoperative changes in the connectome in CHD neonates and assess risk factors for disturbed perioperative network development relative to healthy term newborns. In this prospective cohort study, 114 term neonates with CHD underwent cardiac surgery at the University Children's Hospital Zurich. Forty-six healthy term newborns were included as controls. Pre- and postoperative structural connectomes were derived from mean fractional anisotropy values of fibre pathways traced using diffusion tractography. Graph theory parameters calculated across a range of proportional cost thresholds were compared between groups by multi-threshold permutation correction adjusting for confounders. Network based statistic was calculated for edgewise network comparison. White matter injury (WMI) volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms of (i) CHD subtype and (ii) WMI volume with postmenstrual age at MRI respectively were built to assess modifying effects on network development. Pre- and postoperatively, at the global level, efficiency, indicative of network integration, was higher in controls compared to CHD neonates. In contrast, local efficiency and transitivity, indicative of network segregation, were higher in CHD neonates compared to controls (all p
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.19.304923v1?rss=1 Authors: MENG, L., WANG, C., Shi, Y., LUO, Q. Abstract: There is a strong demand for the methods that can efficiently reconstruct biologically valid super-resolution intact genome 3D structures from sparse and noise single-cell Hi-C data. Here, we developed Single-Cell Chromosome Conformation Calculator (Si-C) within the Bayesian theory framework and applied this approach to reconstruct intact genome 3D structures from the single-cell Hi-C data of eight G1-phase haploid mouse ES cells. The inferred 100-kb and 10-kb structures consistently reproduce the known conserved features of chromatin organization revealed by independent imaging experiments. The analysis of the 10-kb resolution 3D structures revealed cell-to-cell varying domain structures in individual cells and hyperfine structures in domains, such as loops. An average of 0.2 contact reads per divided bin is sufficient for Si-C to obtain reliable structures. The valid super-resolution structures constructed by Si-C demonstrates the potential for visualizing and investigating interactions between all chromatin loci at genome scale in individual cells. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.18.304170v1?rss=1 Authors: Jami, S. A., Cameron, S., Wong, J. M., Daly, E. R., McAllister, A. K., Gray, J. A. Abstract: There is substantial evidence that both NMDA receptor (NMDAR) hypofunction and dysfunction of GABAergic neurotransmission contribute to schizophrenia, though the relationship between these pathophysiological processes remains largely unknown. While models using cell-type-specific genetic deletion of NMDARs have been informative, they display overly pronounced phenotypes extending beyond those of schizophrenia. Here, we used the serine racemase knockout (SRKO) mice, a model of reduced NMDAR activity rather than complete receptor elimination, to examine the link between NMDAR hypofunction and decreased GABAergic inhibition. The SRKO mice, in which there is a >90% reduction in the NMDAR co-agonist D-serine, exhibit many of the neurochemical and behavioral abnormalities observed in schizophrenia. We found a significant reduction in inhibitory synapses onto CA1 pyramidal neurons in the SRKO mice. This reduction increases the excitation/inhibition balance resulting in enhanced synaptically-driven neuronal excitability and elevated broad-spectrum oscillatory activity in ex vivo hippocampal slices. Consistently, significant reductions in inhibitory synapse density in CA1 were observed by immunohistochemistry. We further show, using a single-neuron genetic deletion approach, that the loss of GABAergic synapses onto pyramidal neurons observed in the SRKO mice is driven in a cell-autonomous manner following the deletion of SR in individual CA1 pyramidal cells. These results support a model whereby NMDAR hypofunction in pyramidal cells disrupts GABAergic synapse development leading to disrupted feedback inhibition and impaired neuronal synchrony. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.15.299164v1?rss=1 Authors: Ma, C., Hu, Y., Townsend, J. A., Lagarias, P., Marty, M. T., Kolocouris, A., Wang, J. Abstract: There is an urgent need for vaccines and antiviral drugs to combat the COVID-19 pandemic. Encouraging progress has been made in developing antivirals targeting SARS-CoV-2, the etiological agent of COVID-19. Among the drug targets being investigated, the viral main protease (Mpro) is one of the most extensively studied drug targets. Mpro is a cysteine protease that hydrolyzes the viral polyprotein at more than 11 sites and it is highly conserved among coronaviruses. In addition, Mpro has a unique substrate preference for glutamine in the P1 position. Taken together, it appears that Mpro inhibitors can achieve both broad-spectrum antiviral activity and a high selectivity index. Structurally diverse compounds have been reported as Mpro inhibitors, with several of which also showed antiviral activity in cell culture. In this study, we investigated the mechanism of action of six previously reported Mpro inhibitors, ebselen, disulfiram, tideglusib, carmofur, shikonin, and PX-12 using a consortium of techniques including FRET-based enzymatic assay, thermal shift assay, native mass spectrometry, cellular antiviral assays, and molecular dynamics simulations. Collectively, the results showed that the inhibition of Mpro by these six compounds is non-specific and the inhibition is abolished or greatly reduced with the addition of reducing reagent DTT. In the absence of DTT, these six compounds not only inhibit Mpro, but also a panel of viral cysteine proteases including SARS-CoV-2 papain-like protease, the 2Apro and 3Cpro from enterovirus A71 (EV-A71) and EV-D68. However, none of the compounds inhibits the viral replication of EV-A71 or EV-D68, suggesting that the enzymatic inhibition potency IC50 values obtained in the absence of DTT cannot be used to faithfully predict their cellular antiviral activity. Overall, we provide compelling evidence suggesting that ebselen, disulfiram, tideglusib, carmofur, shikonin, and PX-12 are non-specific SARS-CoV-2 Mpro inhibitors, and urge the scientific community to be stringent with hit validation. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.11.293167v1?rss=1 Authors: Skipper, J. I., Aliko, S., Brown, S., Jo, Y. J., Lo, S., Molimpakis, E., Lametti, D. R. Abstract: There is a widespread assumption that there are a static set of 'language regions' in the brain. Yet, people still regularly produce familiar 'formulaic' expressions when those regions are severely damaged. This suggests that the neurobiology of language varies with the extent of word sequence learning and might not be fixed. We test the hypothesis that perceiving sentences is mostly supported by sensorimotor regions involved in speech production and not 'language regions' after overlearning. Twelve participants underwent two sessions of behavioural testing and functional magnetic resonance imaging (fMRI), separated by 15 days. During this period, they repeated two sentences 30 times each, twice a day. In both fMRI sessions, participants 'passively' listened to those two sentences and novel sentences. Lastly, they spoke novel sentences. Behavioural results confirm that participants overlearned sentences. Correspondingly, there was an increase or recruitment of sensorimotor regions involved in sentence production and a reduction in activity or inactivity for overlearned sentences in regions involved in listening to novel sentences. The global network organization of the brain changed by ~45%, mostly through lost connectivity. Thus, there was a profound reorganization of the neurobiology of speech perception after overlearning towards sensorimotor regions not considered in most contemporary models and away from the 'language regions' posited by those models. These same sensorimotor regions are generally preserved in aphasia and Alzheimer's disease, perhaps explaining residual abilities with formulaic language. These and other results warrant reconsidering static neurobiological models of language. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.02.278119v1?rss=1 Authors: Coffey, E. B., Arseneau-Bruneau, I., Zhang, X., Baillet, S., Zatorre, R. Abstract: There is much debate about the existence and function of neural oscillatory entrainment mechanisms in the auditory system. The frequency-following response (FFR) is an index of neural periodicity encoding that can provide a vehicle to study entrainment in frequency ranges relevant to speech and music processing. Criteria for entrainment include the presence of post-stimulus oscillations and phase alignment between stimulus and endogenous activity. To test the hypothesis of entrainment, in experiment 1 we collected FFR data to a repeated syllable using magneto- (MEG) and electroencephalography in 20 healthy adults. We observed significant oscillatory activity after stimulus offset in auditory cortex and subcortical auditory nuclei, consistent with entrainment. In these structures the FFR fundamental frequency converged from a lower value over 100 ms to the stimulus frequency, consistent with phase alignment, and diverged to a lower value after offset, consistent with relaxation to a preferred frequency. In experiment 2, we tested how transitions between stimulus frequencies affected the MEG-FFR to a train of pure-tone pairs in 30 adults. We found that the FFR was affected by the frequency of the preceding tone for up to 40 ms at subcortical levels, and even longer durations at cortical levels. Our results suggest that oscillatory entrainment may be an integral part of periodic sound representation throughout the auditory neuraxis. The functional role of this mechanism is unknown, but it could serve as a fine-scale temporal predictor for frequency information, enhancing stability and reducing susceptibility to degradation that could be useful in real-life noisy environments. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.24.213447v1?rss=1 Authors: Yamaguchi, H., Hashimoto, Y., Sugihara, G., Miyata, J., Murai, T., Takahashi, H., Honda, M., Hishimoto, A., Yamashita, Y. Abstract: There has been increasing interest in performing psychiatric brain imaging studies using deep learning. However, most studies in this field disregard three-dimensional (3D) spatial information and targeted disease discrimination, without considering the genetic and clinical heterogeneity of psychiatric disorders. The purpose of this study was to investigate the efficacy of a 3D convolutional autoencoder (CAE) for extracting features related to psychiatric disorders without diagnostic labels. The network was trained using a Kyoto University dataset including 82 patients with schizophrenia (SZ) and 90 healthy subjects (HS), and was evaluated using Center for Biomedical Research Excellence (COBRE) datasets including 71 SZ patients and 71 HS. The proposed 3D-CAEs were successfully reconstructed into high-resolution 3D structural magnetic resonance imaging (MRI) scans with sufficiently low errors. In addition, the features extracted using 3D-CAE retained the relevant clinical information. We explored the appropriate hyper parameter range of 3D-CAE, and it was suggested that a model with eight convolution layers might be relevant to extract features for predicting the dose of medication and symptom severity in schizophrenia. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.18.256735v1?rss=1 Authors: Gu, H., Yuan, G. Abstract: There is an urgent need to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) that leads to COVID-19 and respiratory failure. Our study is to discover differentially expressed genes (DEGs) and biological signaling pathways by using a bioinformatics approach to elucidate their potential pathogenesis. The gene expression profiles of the GSE150819 datasets were originally produced using an Illumina NextSeq 500 (Homo sapiens). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) were utilized to identify functional categories and significant pathways. KEGG and GO results suggested that the Cytokine-cytokine receptor interaction, P53 signaling pathway, and Apoptosis are the main signaling pathways in SARS-CoV-2 infected human bronchial organoids (hBOs). Furthermore, NFKBIA, C3, and CCL20 may be key genes in SARS-CoV-2 infected hBOs. Therefore, our study provides further insights into the therapy of COVID-19. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.10.245373v1?rss=1 Authors: He, T., An, L., Feng, J., Bzdok, D., Holmes, A. J., Eickhoff, S. B., Yeo, B. T. T. Abstract: There is significant interest in using brain imaging data to predict non-brain-imaging phenotypes in individual participants. However, most prediction studies are underpowered, relying on less than a few hundred participants, leading to low reliability and inflated prediction performance. Yet, small sample sizes are unavoidable when studying clinical populations or addressing focused neuroscience questions. Here, we propose a simple framework - "meta-matching" - to translate predictive models from large-scale datasets to new unseen non-brain-imaging phenotypes in boutique studies. The key observation is that many large-scale datasets collect a wide range inter-correlated phenotypic measures. Therefore, a unique phenotype from a boutique study likely correlates with (but is not the same as) some phenotypes in some large-scale datasets. Meta-matching exploits these correlations to boost prediction in the boutique study. We applied meta-matching to the problem of predicting non-brain-imaging phenotypes using resting-state functional connectivity (RSFC). Using the UK Biobank (N = 36,848), we demonstrated that meta-matching can boost the prediction of new phenotypes in small independent datasets by 100% to 400% in many scenarios. When considering relative prediction performance, meta-matching significantly improved phenotypic prediction even in samples with 10 participants. When considering absolute prediction performance, meta-matching significantly improved phenotypic prediction when there were least 50 participants. With a growing number of large-scale population-level datasets collecting an increasing number of phenotypic measures, our results represent a lower bound on the potential of meta-matching to elevate small-scale boutique studies. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.11.246355v1?rss=1 Authors: Sohn, H., Jazayeri, M. Abstract: There are two sharply debated views on how humans make decisions under uncertainty. Bayesian decision theory posits that humans optimize their behavior by establishing and integrating internal models of past sensory experiences (priors) and decision outcomes (cost functions). An alternative model-free hypothesis posits that decisions are optimized through trial and error without explicit internal models for priors and cost functions. To distinguish between these possibilities, we introduce a novel paradigm that probes sensitivity of humans to transitions between prior-cost pairs that demand the same optimal policy (metamers) but distinct internal models. We demonstrate the utility of our approach in two experiments that were classically explained by model-based Bayesian theory. Our approach validates the model-based strategy in an interval timing task but not in a visuomotor rotation task. More generally, our work provides a domain-general approach for testing the circumstances under which humans implement model-based Bayesian computations. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.10.244632v1?rss=1 Authors: Aktas, E. Abstract: There are some mutations are known related to SARS-CoV-2. Together with these mutations known, we tried to show other newly mutations regionally. According to our results which 4326 whole sequences are used, we found that some mutations occur only in a certain region, while some other mutations are found in each regions. Especially in Asia, more than one mutation (three different mutations are found in QLA46612 isolated from South Korea) was seen in the same sequence. Although we detected a huge number of mutations (we found more than seventy in Asia) by regions, some of them were predicted that damage spike's protein structure by using bioinformatic tools. The predicted results are G75V (isolated from North America), T95I (isolated from South Korea), G143V (isolated from North America), M177I (isolated Asia), L293M (isolated from Asia), P295H (isolated from Asia), T393P (isolated from Europe), P507S (isolated from Asia), D614G (isolated from all regions) respectively. Also, in this study, we tried to show how possible binding sites of ligands change if the spike protein structure is damaged and whether more than one mutation affects ligand binding was estimated using bioinformatics tools. Interestingly, mutations that predicted to damage the structure do not affect ligand binding sites, whereas ligands' binding sites were affected in those with multiple mutations. Focusing on mutations may opens up the window to exploit new future therapeutic targets. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.04.235994v1?rss=1 Authors: Strausz, S., Ruotsalainen, S. E., Ollila, H. M., Karjalainen, J., Reeve, M., Kurki, M., Mars, N., Havulinna, A. S., Kiiskinen, T., Mansour Aly, D., Ahlqvist, E., Teder-Laving, M., Palta, P., Groop, L., Magi, R., Makitie, A., Salomaa, V., Bachour, A., Tuomi, T., Palotie, A., Palotie, T., Ripatti, S. Abstract: There is currently only limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). The aim of our study is to identify genetic loci associated with OSA risk and to test if OSA and its comorbidities share a common genetic background. We conducted the first large-scale genome-wide association study of OSA using FinnGen Study (217,955 individuals) with 16,761 OSA patients identified using nationwide health registries. We estimated 8.3% [0.06-0.11] heritability and identified five loci associated with OSA (P < 5.0x10^-8): rs4837016 near GTPase activating protein and VPS9 domains 1 (GAPVD1), rs10928560 near C-X-C motif chemokine receptor 4 (CXCR4), rs185932673 near Calcium/calmodulin-dependent protein kinase ID (CAMK1D) and rs9937053 near Fat mass and obesity-associated protein (FTO) - a variant previously associated with body mass index (BMI). In a BMI-adjusted analysis, an association was observed for rs10507084 near Rhabdomyosarcoma 2 associated transcript (RMST)/NEDD1 gamma-tubulin ring complex targeting factor (NEDD1). We found genetic correlations between OSA and BMI (rg=0.72 [0.62-0.83]) and with comorbidities including hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), stroke, depression, hypothyroidism, asthma and inflammatory rheumatic diseases (IRD) (rg > 0.30). Polygenic risk score (PRS) for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile and Mendelian randomization supported a causal relationship between BMI and OSA. Our findings support the causal link between obesity and OSA and joint genetic basis between OSA and comorbidities. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.03.231340v1?rss=1 Authors: Linsky, T. W., Vergara, R., Codina, N., Nelson, J. W., Walker, M. J., Su, W., Hsiang, T.-Y., Esser-Nobis, K., Yu, K., Hou, Y. J., Priya, T., Mitsumoto, M., Pong, A., Lau, U. Y., Mason, M. L., Chen, J., Chen, A., Berrocal, T., Peng, H., Clairmont, N. S., Castellanos, J., Lin, Y.-R., Josephson-Day, A., Baric, R. S., Walkey, C. D., Swanson, R., Blancas-Mejia, L. M., Gale, M., Yen, H.-L., Silva, D.-A. Abstract: There is an urgent need for the ability to rapidly develop effective countermeasures for emerging biological threats, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a generalized computational design strategy to rapidly engineer de novo proteins that precisely recapitulate the protein surface targeted by biological agents, like viruses, to gain entry into cells. The designed proteins act as decoys that block cellular entry and aim to be resilient to viral mutational escape. Using our novel platform, in less than ten weeks, we engineered, validated, and optimized de novo protein decoys of human angiotensin-converting enzyme 2 (hACE2), the membrane-associated protein that SARS-CoV-2 exploits to infect cells. Our optimized designs are hyperstable de novo proteins (~18-37 kDa), have high affinity for the SARS-CoV-2 receptor binding domain (RBD) and can potently inhibit the virus infection and replication in vitro. Future refinements to our strategy can enable the rapid development of other therapeutic de novo protein decoys, not limited to neutralizing viruses, but to combat any agent that explicitly interacts with cell surface proteins to cause disease. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.220442v1?rss=1 Authors: Powell, D. J., Marder, E., Nusbaum, M. P. Abstract: There is considerable flexibility embedded within neural circuits. For example, separate modulatory inputs can differently configure the same underlying circuit but these different configurations generate comparable, or degenerate, activity patterns. However, little is known about whether these mechanistically different circuits in turn exhibit degenerate responses to the same inputs. We examined this issue using the crab (Cancer borealis) stomatogastric nervous system, in which stimulating the modulatory projection neuron MCN1 and bath applying the neuropeptide CabPK II elicit similar gastric mill (chewing) rhythms in the stomatogastric ganglion, despite differentially configuring the same neural circuit. We showed previously that bath applying the peptide hormone CCAP or stimulating the muscle stretch-sensitive sensory neuron GPR during the MCN1-elicited gastric mill rhythm selectively prolongs the protraction or retraction phase, respectively. Here, we found that these two influences on the CabPK-rhythm elicited some unique and unexpected consequences compared to their actions on the MCN1-rhythm. For example, in contrast to its effect on the MCN1-rhythm, CCAP selectively decreased the CabPK-rhythm retraction phase and thus increased the rhythm speed, whereas the CabPK-rhythm response to stimulating GPR during the retraction phase was similar its effect on the MCN1-rhythm (i.e. prolonging retraction). Interestingly, despite the comparable GPR actions on these degenerate rhythms, the underlying synaptic mechanism was distinct. Thus, degenerate circuits do not necessarily exhibit degenerate responses to the same influence, but when they do, it can occur via different underlying mechanisms. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.219857v1?rss=1 Authors: Esparza, T. J., Brody, D. L. Abstract: There are currently no approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12-15 kDa single-domain antibody fragments that are more stable and amenable to large-scale production compared to conventional antibodies. Nanobodies can also be administered in an inhaled form directly to the lungs. We have isolated several nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) receptor. The SARS-CoV-2 spike protein is responsible for viral entry into human cells via interaction with ACE2 on the cell surface. The lead therapeutic candidate, NIH-CoVnb-112, binds to the SARS-CoV-2 spike protein receptor binding domain at approximately 5 nM affinity, and blocks spike protein interaction with the human ACE2 receptor at approximately 0.02 micrograms/mL EC50 (1.1 nM). The affinity and blocking potency of NIH-CoVnb-112 are substantially better than previously reported candidate nanobody therapeutics for SARS CoV-2, and bind to a distinct site. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. When multimerized or combined with other nanobodies, the effective affinity and blocking interactions may be even more potent, as has been well described for other nanobody therapeutics. These resulting nanobodies have therapeutic, preventative, and diagnostic potential. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.01.183038v1?rss=1 Authors: Cole, M., Murray, K. D., St-Onge, E., Risk, B., Zhong, J., Schifitto, G., Descoteaux, M., Zhang, Z. Abstract: There has been increasing interest in jointly studying structural connectivity (SC) and functional connectivity (FC) derived from diffusion and functional MRI. However, several fundamental problems are still not well considered when conducting such connectome integration analyses, e.g., "Which structure (e.g., gray matter, white matter, white surface or pial surface) should be used for defining SC and FC and exploring their relationships", "Which brain parcellation should be used", and "How do the SC and FC correlate with each other and how do such correlations vary in different locations of the brain?". In this work, we develop a new framework called surface-based connectivity integration (SBCI) to facilitate the integrative analysis of SC and FC with a re-thinking of these problems. We propose to use the white surface (the interface of white matter and gray matter) to build both SC and FC since diffusion signals are in the white matter while functional signals are more present in the gray matter. SBCI also represents both SC and FC in a continuous manner at very high spatial resolution on the white surface, avoiding the need of pre-specified atlases which may bias the comparison of SC and FC. Using data from the Human Connectome Project, we show that SBCI can create reproducible, high quality SC and FC, in addition to three novel imaging biomarkers reflective of the similarity between SC and FC throughout the brain, called global, local, and discrete SC-FC coupling. Further, we demonstrate the usefulness of these biomarkers in finding group effects due to biological sex throughout the brain. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.29.178970v1?rss=1 Authors: Karimi-Rouzbahani, H., Woolgar, A., Rich, A. N. Abstract: There are now many environments in which humans need to monitor moving displays and only rarely act, such as train control and driving autonomous vehicles; lapses of attention in these circumstances can have tragic consequences. Problematically, we know that it is difficult to sustain attention under these monitoring or vigilance conditions and performance drops: when target events are rare, we tend to miss them, or are slower to respond. This "rare target" effect becomes more marked with longer tasks, known as a vigilance decrement. Despite the importance, we still have limited understanding of how the brain processes information during monitoring, particularly with dynamic stimuli, and how this processing changes when attention lapses. Here, we designed a multiple-object monitoring (MOM) paradigm that required sustained attention to dynamic stimuli, and used multivariate analyses of magnetoencephalography (MEG) data to examine how the neural representation of the information in the display varied with target frequency and time on the task. Behavioural performance decreased over time for the rare target (monitoring) condition, but not for the frequent target (active) condition. This change was mirrored in the neural results: under monitoring conditions, there was weaker coding of the critical distance between objects during time periods when vigilance decrements in performance occurred. There was also weaker informational connectivity between peri-occipital and peri-frontal brain areas in rare versus frequent target conditions. We developed a new analysis which used the strength of information decoding to predict whether the participant was going to miss the target on a given trial. We could predict behavioural errors more than a second before they occurred. This provides a first step in developing methods to predict and pre-empt behavioural errors due to lapses in attention and provides new insight into how vigilance decrements are reflected in information coding in the brain. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.27.175133v1?rss=1 Authors: Daws, R. E., Soreq, E., Li, Y., Sandrone, S., Hampshire, A. Abstract: There is an unresolved discrepancy between popular hierarchical and multiple-demand perspectives on the functional organisation of the human frontal lobes. Here, we tested alternative predictions of these perspectives with a novel fMRI switching paradigm. Each trial involved switching attention between stimuli, but at different levels of difficulty and abstraction. As expected, increasing response times were evident when comparing low-level perceptual switching to more abstract dimension, rule and task-switching. However, there was no evidence of an abstraction hierarchy within the prefrontal cortex (PFC). Nor was there recruitment of additional anterior PFC regions under increased switching demand. Instead, switching activated a widespread network of frontoparietal and cerebellar regions. Critically, the activity within PFC sub-regions uniformly increased with behavioural switch costs. We propose that both perspectives have some validity, but neither is complete. Too many studies have reported dissociations within MD for this volume to be functionally uniform, and the recruitment of more anterior regions with increased general difficulty cannot explain those results. Conversely, whilst reproducible evidence for a hierarchical functional organisation has been reported, this cannot be explained in terms of abstraction of representation or reconfiguration per se, because those interpretations generalise poorly to other task contexts. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.136598v1?rss=1 Authors: Emerson, N. M., Nahman-Averbuch, H., Coghill, R. C. Abstract: There is emerging evidence suggesting a relationship between obesity and chronic pain. We investigated whether pain-free obese individuals display altered pain responses to acute noxious stimuli, thus raising the possibility of greater pain sensitivity and potential susceptibility for chronic pain development. Psychophysical and anthropometric data were collected from 39 individuals with an obese body mass index (BMI) classification (BMI [≥] 30) and 40 age/sex-matched individuals of a healthy BMI (BMI
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.26.117507v1?rss=1 Authors: Bowman, C. R., Iwashita, T., Zeithamova, D. Abstract: There has been a long-standing debate about whether categories are represented by individual category members (exemplars) or by the central tendency abstracted from individual members (prototypes). Across neuroimaging studies, there has been neural evidence for either exemplar representations or prototype representations, but not both. In the present study, we asked whether it is possible for individuals to form multiple types of category representations within a single task. We designed a categorization task to promote both exemplar and prototype representations, and we tracked their formation across learning. We found evidence for co-existing prototype and exemplar representations in brain in regions that aligned with previous studies: prototypes in ventromedial prefrontal cortex and anterior hippocampus and exemplars in inferior frontal gyrus and lateral parietal cortex. These findings show that, under the right circumstances, individuals may form representations at multiple levels of specificity, potentially facilitating a broad range of future memory-based decisions. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.03.129627v1?rss=1 Authors: Rodgers, J., Bano-Otalora, B., Belle, M. D., Paul, S., Hughes, R., Wright, P., McDowell, R., Milosavljevic, N., Orlowska-Feuer, P., Martial, F., Wynne, J., Ballister, E. R., Storchi, R., Allen, A. E., Brown, T., Lucas, R. J. Abstract: There is no consensus on the best optogenetic tool for inhibiting neural activity. Lamprey parapinopsin (Lamplight) is a Gi/o-coupled bistable animal opsin that can be activated and deactivated by short and long wavelength light, respectively. Since native mechanisms of neuronal inhibition frequently employ Gi/o signalling, we asked here whether Lamplight could be used for optogenetic silencing. We show that brief short (405nm) and long (525nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, and that combining these wavelengths can be used to achieve intermediate levels of activity. We demonstrate that these properties can be applied to produce switchable and scalable neuronal hyperpolarisation, and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. We show that expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, and that 405 and 525nm stimuli can produce responses of opposite sign in output neurons of the retina. Lamplight-driven responses to both activating (405nm) and deactivating (525nm) light can occur within 500ms. We conclude that Lamplight can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and rapidly reversible. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.27.117226v1?rss=1 Authors: Perez, D. L., Bokde, A. L. W., Kerskens, C. Abstract: There are multiple magnet resonance imaging (MRI) based approaches to studying the ageing brain. Getting older affects both the structure of the brain and our cognitive capabilities but there is still no solid evidence on how ageing influences the mechanisms underlying the MRI signal. Here, we apply a recently developed long-range zero-quantum coherence (ZQC) weighted MRI sequence that was found to be sensitive to wakefulness. We found that the complexity of the signal time curve is also affected by age. While comparing young and old participants, we found qualitative and quantitative evidence that the dynamics of these quantum fluctuations undergo strong changes with age. Finally, we study how differences in long-range ZQC relate with measures from different cognitive batteries, suggesting that long-range ZQC may be key for cerebral dynamics and cognitive functioning. The profound sensitivity for dynamic changes shows the potential of long-range ZQC and its underlying physiological mechanism with clinical relevance for all neurovascular diseases. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.101618v1?rss=1 Authors: Klauser, A., Klauser, P., Grouiller, F., Courvoisier, S., Lazeyras, F. Abstract: There is a growing interest of the neuroscience community to map the distribution of brain metabolites in vivo. Magnetic resonance spectroscopy imaging (MRSI) is often limited by either a poor spatial resolution and/or a long acquisition time which severely limits its applications for clinical or research purposes. We developed a novel acquisition-reconstruction technique combining fast 1H-FID-MRSI sequence accelerated by random k-space undersampling and a low-rank and total-generalized variation (TGV) constrained model. This framework was applied to the brain of four healthy volunteers. Following 20 min acquisition, reconstruction and quantification, the resulting metabolic maps with a 5mm isotropic resolution reflected the detailed neurochemical composition of all brain regions and revealed part of the underlying brain anatomy. Contrasts and features from the 3D metabolite distributions were in agreement with the literature and consistent across the four subjects. The successful combination of the 3D 1H-FID-MRSI with a constrained reconstruction enables the detailed mapping of metabolite concentrations at high-resolution in the whole brain and with an acquisition time that is compatible with clinical or research settings. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.101881v1?rss=1 Authors: Lian, Y., Almasi, A., Grayden, D. B., Kameneva, T., Burkitt, A. N., Meffin, H. Abstract: There are two distinct classes of cells in the primary visual cortex (V1): simple cells and complex cells. One defining feature of complex cells is their spatial phase invariance; they respond strongly to oriented grating stimuli with a preferred orientation but with a wide range of spatial phases. A classical model of complete spatial phase invariance in complex cells is the energy model, in which the responses are the sum of the squared outputs of two linear spatially phase-shifted filters. However, recent experimental studies have shown that complex cells have a diverse range of spatial phase invariance and only a subset can be characterized by the energy model. While several models have been proposed to explain how complex cells could learn to be selective to orientation but invariant to spatial phase, most existing models overlook many biologically important details. We propose a biologically plausible model for complex cells that learns to pool inputs from simple cells based on the presentation of natural scene stimuli. The model is a three-layer network with rate-based neurons that describes the activities of LGN cells (layer 1), V1 simple cells (layer 2), and V1 complex cells (layer 3). The first two layers implement a recently proposed simple cell model that is biologically plausible and accounts for many experimental phenomena. The neural dynamics of the complex cells is modeled as the integration of simple cells inputs along with response normalization. Connections between LGN and simple cells are learned using Hebbian and anti-Hebbian plasticity. Connections between simple and complex cells are learned using a modified version of the Bienenstock, Cooper, and Munro (BCM) rule. Our results demonstrate that the learning rule can describe a diversity of complex cells, similar to those observed experimentally. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.101873v1?rss=1 Authors: Lian, Y., Almasi, A., Grayden, D. B., Kameneva, T., Burkitt, A. N., Meffin, H. Abstract: There are two distinct classes of cells in the primary visual cortex (V1): simple cells and complex cells. One defining feature of complex cells is their spatial phase invariance; they respond strongly to oriented grating stimuli with a preferred orientation but with a wide range of spatial phases. A classical model of complete spatial phase invariance in complex cells is the energy model, in which the responses are the sum of the squared outputs of two linear spatially phase-shifted filters. However, recent experimental studies have shown that complex cells have a diverse range of spatial phase invariance and only a subset can be characterized by the energy model. While several models have been proposed to explain how complex cells could learn to be selective to orientation but invariant to spatial phase, most existing models overlook many biologically important details. We propose a biologically plausible model for complex cells that learns to pool inputs from simple cells based on the presentation of natural scene stimuli. The model is a three-layer network with rate-based neurons that describes the activities of LGN cells (layer 1), V1 simple cells (layer 2), and V1 complex cells (layer 3). The first two layers implement a recently proposed simple cell model that is biologically plausible and accounts for many experimental phenomena. The neural dynamics of the complex cells is modeled as the integration of simple cells inputs along with response normalization. Connections between LGN and simple cells are learned using Hebbian and anti-Hebbian plasticity. Connections between simple and complex cells are learned using a modified version of the Bienenstock, Cooper, and Munro (BCM) rule. Our results demonstrate that the learning rule can describe a diversity of complex cells, similar to those observed experimentally. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.15.098269v1?rss=1 Authors: Fritz, F. J., Poser, B. A., Roebroeck, A. Abstract: There is an increasing interest in quantitative imaging of T1, T2 and diffusion contrast in the brain due to greater robustness against bias fields and artifacts, as well as better biophysical interpretability in terms of microstructure. However, acquisition time constraints are a challenge, particularly when multiple quantitative contrasts are desired and when extensive sampling of diffusion directions, high b-values or long diffusion times are needed for multi-compartment microstructure modeling. Although ultra-high fields of 7 T and above have desirable properties for many MR modalities, the shortening T2 and the high specific absorption rate (SAR) of inversion and refocusing pulses bring great challenges to quantitative T1, T2 and diffusion imaging. Here, we present the MESMERISED sequence (Multiplexed Echo Shifted Multiband Excited and Recalled Imaging of STEAM Encoded Diffusion). MESMERISED removes the dead time in Stimulated Echo Acquisition Mode (STEAM) imaging by an echo-shifting mechanism. The echo-shift (ES) factor is independent of multiband (MB) acceleration and allows for very high multiplicative (ESxMB) acceleration factors, particularly under moderate and long mixing times. This results in high duty cycle and time efficiency at 7 T, particularly for quantitative T1 and diffusion imaging, while also retaining the capacity to perform quantitative T2 and B1 mapping. We demonstrate the super-acceleration of MESMERISED for whole-brain T1 relaxometry with total acceleration factors up to 36 at 1.8 mm isotropic resolution, and up to 54 at 1.25 mm resolution qT1 imaging, corresponding to a 6x and 9x speed-up, respectively, compared to MB-only accelerated acquisitions. We demonstrate quantitative T2 and B1 mapping to illustrate multi-contrast mapping with the same MESMERISED sequence and the same readout train. Finally, we demonstrate highly efficient diffusion MRI with high b-values and long diffusion times in two separate cases. First, we show that super-accelerated multi-shell diffusion acquisitions with 370 whole-brain diffusion volumes over 8 b-value shells up to b = 7000 s/mm2 can be generated at 2 mm isotropic in under 8 minutes, a data rate of almost a volume per second, or at 1.8 mm isotropic in under 11 minutes. Second, we demonstrate time-efficient sampling of different diffusion times with 1.8 mm isotropic diffusion data acquired at four diffusion times up to 290 ms, which supports both Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI) at each diffusion time. MESMERISED extends possibilities to efficiently probe T1, T2 and diffusion contrast for multi-component modeling of tissue microstructure. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.089144v1?rss=1 Authors: Antonovaite, N., Hulshof, L. A., Hol, E. M., Wadman, W. J., Iannuzzi, D. Abstract: There is growing evidence that mechanical factors affect brain functioning. However, brain components responsible for regulating the physiological mechanical environment and causing mechanical alterations during maturation are not completely understood. To determine the relationship between structure and stiffness of the brain tissue, we performed high resolution viscoelastic mapping by dynamic indentation of hippocampus and cerebellum of juvenile brain, and quantified relative area covered by immunohistochemical staining of NeuN (neurons), GFAP (astrocytes), Hoechst (nuclei), MBP (myelin), NN18 (axons) of juvenile and adult mouse brain slices. When compared the mechanical properties of juvenile mouse brain slices with previously obtained data on adult slices, the latter was ~20-150% stiffer, which correlates with an increase in the relative area covered by astrocytes. Heterogeneity within the slice, in terms of storage modulus, correlates negatively with the relative area of nuclei and neurons, as well as myelin and axons, while the relative area of astrocytes correlates positively. Several linear regression models are suggested to predict the mechanical properties of the brain tissue based on immunohistochemical stainings. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.30.066407v1?rss=1 Authors: Liu, Y., Dolan, R., Kurth-Nelson, Z., Behrens, T. E. J. Abstract: There are rich structures in off-task neural activity. For example, task related neural codes are thought to be reactivated in a systematic way during rest. This reactivation is hypothesised to reflect a fundamental computation that supports a variety of cognitive functions. Here, we introduce an analysis toolkit (TDLM) for analysing this activity. TDLM combines nonlinear classification and linear temporal modelling to testing for statistical regularities in sequences of neural representations. It is developed using non-invasive neuroimaging data and is designed to take care of confounds and maximize sequence detection ability. The method can be extended to rodent electrophysiological recordings. We outline how TDLM can successfully reveal human replay during rest, based upon non-invasive magnetoencephalography (MEG) measurements, with strong parallels to rodent hippocampal replay. TDLM can, therefore, advance our understanding of sequential computation and promote a richer convergence between animal and human neuroscience research. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.23.056929v1?rss=1 Authors: McInnes, A. N., Castellote, J. M., Kofler, M., Honeycutt, C. F., Lipp, O. V., Riek, S., Tresilian, J. R., Marinovic, W. Abstract: There has been much debate concerning whether startling sensory stimuli can activate a fast-neural pathway for movement triggering (StartReact) which is different from that of voluntary movements. Activity in sternocleidomastoid (SCM) electromyogram is suggested to indicate activation of this pathway. We evaluated whether SCM activity can accurately identify trials which may differ in their neurophysiological triggering and assessed the use of cumulative distribution functions (CDFs) of reaction time (RT) data to identify trials with the shortest RTs for analysis. Using recent datasets from the StartReact literature, we examined the relationship between RT and SCM activity. We categorised data into short/longer RT bins using CDFs and used linear mixed effects models to compare potential conclusions that can be drawn when categorising data on the basis of RT versus on the basis of SCM activity. The capacity of SCM to predict RT is task-specific, making it an unreliable indicator of distinct neurophysiological mechanisms. Classification of trials using CDFs is capable of capturing potential task- or muscle- related differences in triggering whilst avoiding the pitfalls of the traditional SCM activity based classification method. We conclude that SCM activity is not always evident on trials that show the early triggering of movements seen in the StartReact phenomenon. We further propose that a more comprehensive analysis of data may be achieved through the inclusion of CDF analyses. These findings have implications for future research investigating movement triggering as well as for potential therapeutic applications of StartReact. Copy rights belong to original authors. Visit the link for more info
Abstract: There is a kinship between Lehi and Joseph Smith. They are linked to each other by similar first visions, and they faced roughly the same theological problem. Resisted by elites who believe God is a Solitary Sovereign, both prophets affirm the pluralistic religion of Abraham, which features a sôd ’ĕlôhim (Council of Gods) in which the divine Father, Mother, […]
Abstract: There is a kinship between Lehi and Joseph Smith. They are linked to each other by similar first visions, and they faced roughly the same theological problem. Resisted by elites who believe God is a Solitary Sovereign, both prophets affirm the pluralistic religion of Abraham, which features a sôd ’ĕlôhim (Council of Gods) in which the divine Father, Mother, […]
PDF feed of Interpreter: A Journal of Latter-day Saint Faith and Scholarship
Abstract: There is a kinship between Lehi and Joseph Smith. They are linked to each other by similar first visions, and they faced roughly the same theological problem. Resisted by elites who believe God is a Solitary Sovereign, both prophets affirm the pluralistic religion of Abraham, which features a sôd ’ĕlôhim (Council of Gods) in which the divine Father, Mother, […]
Stephan Hartmann (Tilburg) gives a talk at the Workshop on Mathematical Philosophy titled "Voting, Deliberation and Truth". Abstract: There are various ways to reach a group decision. One way is to simply vote and decide what the majority votes for. This procedure receives some epistemological support from the Condorcet Jury Theorem. Alternatively, the group members may prefer to deliberate and will eventually reach a decision that everybody endorses -- a consensus. While the latter procedure has the advantage that it makes everybody happy (as everybody endorses the consensus), it has the disadvantage that it is difficult to implement, especially for larger groups. What is more, a deliberation is easy to bias as those group members who make others change their mind may not necessarily be the best truth-trackers. But even if no such biases are present, the consensus may be far away from the truth. And so we ask: When is deliberation a better method to track the truth than simple majority voting? To address this question, we propose a Bayesian model of rational non-strategic deliberation and compare it to the straight forward voting procedure. The talk is based on joint work with Soroush Rafiee Rad.
Radin Dardashti (MCMP/LMU) gives a talk at the MCMP Colloquium (2 July, 2014) titled "On the Distinction between Internal and External Symmetries". Abstract: There is no doubt that symmetries play an important role in fundamental physics, but there is no agreement among physicists on what this role exactly is. So it is not surprising that it has caught the interest of philosophers in recent years leading to a lively discussion on the epistemological and ontological significance of symmetries. Especially in this context it becomes relevant whether common distinctions made between different kinds of symmetries are purely conventional or have a deeper mathematical and/or physical justification. It is the aim of this talk to discuss the distinction between internal and external (or spacetime) symmetries and its possible justification. First, I will discuss attempts at combining internal and external symmetries, which lead to several no-go theorems. A naive interpretation of these results leads to the conclusion that the distinction is physically/mathematically justified. Second, the strong dependence of the no-go results on physical and mathematical assumptions is discussed and it is shown how the distinction becomes blurred once mathematical assumptions are weakened. This is exactly what happens in supersymmetric extensions of the standard model of particle physics. So, in the final part, I will argue that under a certain (philosophical) assumption the question about the status of the distinction can be made into an experimental question.
Sam Sanders (MCMP/LMU) gives a talk at the MCMP Colloquium (26 November, 2015) titled "The Unreasonable Effectiveness of Nonstandard Analysis". Abstract: There is a persistent belief, propagated by such luminaries as Errett Bishop and Alain Connes, that infinitesimals (in the sense of Robinson’s Nonstandard Analysis (NSA) ) somehow are fundamentally non-constructive and that NSA is devoid of numerical meaning, as Bishop was wont to say. In this talk, we disprove the Bishop-Connes claim regarding NSA. To this end, we show that theorems of NSA are equivalent to their associated “highly constructive" theorems from numerical analysis (not involving NSA). We shall focus on potential applications of these results in philosophy and computer science, especially concerning vagueness and ontology.
Professor Peter Gregory, the Jill Ker Conway of Professor Emeritus of Religion and East Asian Studies of Smith College, will present a public lecture on "Bridging the Gap: Zongmi’s Strategies for Reconciling Textual Study and Meditative Practice." Abstract: There is a long-standing and deep-rooted tension between what could be characterized as meditative practice and textual study that runs through the Buddhist tradition. It emerges with the early com¬munities, is manifested in different forms throughout the history of the tradition, and is very much alive today. This lecture will examine some of the ways in which this tension plays out in Zongmi’s most ambitious, original, and systematically articulated work, “The General Preface to the Collected Writings on the Source of Chan” (禪源諸詮集都序), written in 833. This work is most famous for its multifaceted attempt to reconcile the doctrinal teachings of the different “philosophical” schools (such as Huayan) with the different traditions of Chan prevalent in his day. The lecture will interrogate this issue by offering a close reading of a critical passage at the beginning of the Preface, where Zongmi lays out his main, overarching reason for composing the text. This passage is of special interest because in it Zongmi gives an account of what might be called an “enlightenment experience” that he had, which provides the basis on which he claims unique authority to be able to resolve the central problem that the text addresses: to bridge the gap between textualists and meditators so as to make the tradition whole again.
Bernard Grofman (Irvine) gives a talk at the MCMP Colloquium (13 May, 2015) titled "Predicting Outcomes in Five Person Spatial Games: An Aspiration Model Approach". Abstract: There are many situations where voters must choose a single alternative and where both the voters and the alternatives can be characterized as points in a one or two or more dimensional policy space. In committees and legislatures, often choice among these alternatives will be done via a decision agenda in which alternatives are eliminated until a choice is made, sometimes requiring a final vote against the status quo. A common form for such an agenda is what has been called by Black (1958) standard amendment procedure, a “king of the hill” procedure in which there is an initial alternative who is paired against another alternative, with the winner of that pairwise contest becoming the new winner, and the processes continuing until either the set of feasible alternatives is exhausted or there is a successful motion for cloture. Beginning with a seminal experiment on five person voting games conducted by Plott and Fiorina (1978), there have been a number of experiments on committee voting games with an potentially infinite set of alternatives embedded in a two dimensional policy space. In games where there is a core, i.e., an alternative which, for an odd number of voters, can defeat each and every other alternative in paired comparison, outcomes at or near the core are chosen, but there is also considerable clustering of outcomes even in games without a core. A major concern of the literature has been to develop models to explain the pattern of that clustering in non-core situations. Here, after reviewing the present state of the art, we offer a new family of models based on the Siegel-Simon aspiration approach, in which voters satisfice by choosing “acceptable” alternative, and the set of outcomes that are considered acceptable by each voter changes as the game continues.
Hannes Leitgeb (MCMP/LMU) gives a talk at the Workshop on Mathematics: Objectivity by Representation (11 November, 2014) titled "On Mathematical Structuralism. A Theory of Unlabeled Graphs as Ante Rem Structures". Abstract: There are different versions of structuralism in present-day philosophy of mathematics which all take as their starting point the structural turn that mathematics took in the last two centuries. In this talk, I will make one variant of structuralism—ante rem structuralism—precise in terms of an axiomatic theory of unlabeled graphs as ante rem structures. I will then use that axiomatic theory in order to address some of the standard objections to ante rem structuralism that one can find in the literature. Along the way, I will discuss also other versions of mathematical structuralism, and I will say something on how the emerging theory of ante rem structures relates to modern set theory.
Elanor Taylor (Iowa) gives a talk at the MCMP conference "Reduction and Emergence in the Sciences" (14-16 November, 2013) titled "An Explication of Emergence". Abstract: There is a consensus in contemporary philosophy that debates about emergence are confused and messy. In this paper I offer a unified explication of emergence, and argue that this explication can cut through the confusion evident in discussions of emergence. I argue that the best way to understand the concept of emergence is as the unavailability of a certain kind of scientific explanation for an observer or observers. According to this perspectival account of emergence, emergence (the unavailability of a certain kind of scientific explanation for an observer or observers) can track a range of different metaphysical and epistemic relations.
James Owen Weatherall (California) gives a talk at the MCMP Colloquium (19 July, 2013) titled "Inertial Motion, Explanation, and the Foundations of Classical Spacetime Theories". Abstract: There is an influential view in physics and philosophy of physics, originating with Einstein and Eddington, that holds that general relativity is distinctive in the history of physics because it can be used to "explain" inertial, or unforced, motion. In this talk, I will describe how a reformulation of Newtonian gravitation may be used to provide insight into claims concerning the (allegedly) distinctive explanatory resources of relativity theory. I will then argue that Newtonian gravitation can be understood to explain inertial motion in much the same way as general relativity. However, a careful comparative study of the status of inertial motion in the two theories reveals that neither explanation is as clean or straightforward as adherents to the view noted above believe. I will conclude by presenting a view about the interdependencies of the central principles of physical theories that I will argue provides some insight into a sense in which inertial motion is explained in both of these theories.
Thomas Ryckman (Stanford) gives a talk at the MCMP workshop "Influences on the Aufbau" (1-3 July, 2013) titled "What Carnap might have learned from Weyl". Abstract: There are easily discernible traces of the influence of Hermann Weyl in the writings of Carnap in the early to mid- 1920s. It is somewhat more difficult to find any palpable influence of Weyl in the Aufbau. On the other hand, Weyl’s 1926 Philosophie der Mathematik und Naturwissenschaften is the sole work singled out in Aufbau's Bibliography as “especially suitable for study of problems connected with construction theory” in both the “logical” and the “epistemological” categories. I shall argue that, in the crucial Aufbau passage (§176) “demonstrating” the non-constructability of the reality (as mind- transcendent) concept, Carnap may have had §17 of Weyl’s 1926 book very much in mind.
Eric Winsberg (USF) gives a talk at the MCMP Colloquium (29 May, 2013) titled "Values and Uncertainties". Abstract: There has been a great deal of emphasis, in recent years, on developing methods for quantifying uncertainty in the predictions of global and regional climate models. Such an approach would allow a division of labor between those who discover the facts and those who decide what we should value. And it is in line with a famous defense of scientific objectivity due to Richard Jeffrey. I argue, however, that value neutral probabilities for climate model projections will be hard to come by in the foreseeable future. In this paper I consider a variety of alternative proposals for presenting what we know about the future from climate models. I suggest that any such proposal ought to take account of " risk aversion" and "ambiguity aversion."
Thomas Forster (Cambridge) gives a talk at the MCMP Colloquium (16 May, 2012) about Quine's "New Foundations". Abstract: There are rumours circulating that Quine's axiomatic set theory "New Foundations" has been proved consistent. If these rumours are correct the set theoretic landscape will have its most radical revamp for more than half a century, and we will all need to re-tool. This talk will provide historical background and glimpse into how the result might be proved.
Abstract: There are many probes for the nature of the dark matter, from high energy cosmic rays, gamma rays, and nuclear recoils in underground detectors. I describe the recent hints for the nature of the dark matter, and discuss prospects for its discovery. Dr. Zurek works at the interface of particle physics with cosmology and astrophysics. Her work spans both studies of new physics signatures at colliders, as well as astrophysical searches for dark matter (DM) and physics beyond the Standard Model in the neutrino sector. Recently, she has been most active in the study of DM. The presence of DM (five times as prevalent as ordinary matter in the universe) provides strong evidence that there are new particles beyond those in the Standard Model (which describes all currently known particles and interactions). Professor Zurek works on theories of DM and ways that we can detect it in the lab by DM-nucleus interactions, at colliders through high energy collisions, and in the galaxy by DM self-annihilations. His lecture was given on March 4, 2011.
ABSTRACT: There are certain universal conditions of a city and of housing that, if codified, can help architects and planners achieve a successful outcome. 'Urbanity', by contrast, as Richard Sennett argues is the making use of differences in a city to help people achieve a balanced sense of identification as well as a view on risk taking. In mæ's work we consider how codes, patterns and computational methodologies or parametric modeling assist or hinder design opportunity and what are the implications for the people that we design for? BIOGRAPHY: Alex Ely is an Architect and founding partner at mæ LLP Architects. He is a CABE Enabler, Building for Life Assessor and former Senior Policy adviser at CABE. Alex leads the mæ's work on sustainable urbanism and housing, working with a wide range of local authorities, public agencies and Housing Associations on housing regeneration, masterplanning, and new build housing design. He has written a number of best practice publications including The London Mayor's Housing Design Guide, CABE's Building for Life Standard and accompanying publication 'Delivering Great Places to Live' and 'The Home Buyer"s Guide'. Alex lectures internationally on design and policy.